rs9478314

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.12795-12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,608,436 control chromosomes in the GnomAD database, including 172,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18122 hom., cov: 33)

Exomes 𝑓: 0.45 ( 154276 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Splicing: ADA: 0.00005298

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.0950

Publications

10 publications found

Variant links:

Genes affected

SYNE1 (HGNC:17089): (spectrin repeat containing nuclear envelope protein 1) This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

SYNE1 Gene-Disease associations (from GenCC):

autosomal recessive ataxia, Beauce type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
arthrogryposis multiplex congenita 3, myogenic type
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Emery-Dreifuss muscular dystrophy 4, autosomal dominant
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
autosomal dominant Emery-Dreifuss muscular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive myogenic arthrogryposis multiplex congenita
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SYNE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-152331902-T-C is Benign according to our data. Variant chr6-152331902-T-C is described in ClinVar as Benign. ClinVar VariationId is 262160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.12795-12A>G		intron_variant	Intron 77 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SYNE1	ENST00000367255.10 link	c.12795-12A>G	intron_variant	Intron 77 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6 link	c.12582-12A>G	intron_variant	Intron 76 of 145	1		ENSP00000396024.1
SYNE1	ENST00000490135.6 link	n.141-12A>G	intron_variant	Intron 1 of 10	1

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

73070

AN:

152010

Hom.:

18103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.550

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.458

Gnomad OTH

AF:

0.477

GnomAD2 exomes

AF:

0.468

AC:

115505

AN:

246858

AF XY:

0.458

show subpopulations

Gnomad AFR exome

AF:

0.540

Gnomad AMR exome

AF:

0.673

Gnomad ASJ exome

AF:

0.549

Gnomad EAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.458

Gnomad NFE exome

AF:

0.462

Gnomad OTH exome

AF:

0.468

GnomAD4 exome

AF:

0.455

AC:

662596

AN:

1456308

Hom.:

154276

Cov.:

AF XY:

0.453

AC XY:

328383

AN XY:

724826

show subpopulations

African (AFR)

AF:

0.529

AC:

17706

AN:

33474

American (AMR)

AF:

0.661

AC:

29574

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.555

AC:

14514

AN:

26134

East Asian (EAS)

AF:

0.200

AC:

7935

AN:

39700

South Asian (SAS)

AF:

0.399

AC:

34377

AN:

86248

European-Finnish (FIN)

AF:

0.455

AC:

21963

AN:

48258

Middle Eastern (MID)

AF:

0.430

AC:

2476

AN:

5764

European-Non Finnish (NFE)

AF:

0.456

AC:

507209

AN:

1111654

Other (OTH)

AF:

0.445

AC:

26842

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

20157

40315

60472

80630

100787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15218

30436

45654

60872

76090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.481

AC:

73128

AN:

152128

Hom.:

18122

Cov.:

AF XY:

0.478

AC XY:

35566

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.540

AC:

22392

AN:

41472

American (AMR)

AF:

0.585

AC:

8938

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.550

AC:

1910

AN:

3472

East Asian (EAS)

AF:

0.157

AC:

814

AN:

5180

South Asian (SAS)

AF:

0.373

AC:

1799

AN:

4822

European-Finnish (FIN)

AF:

0.444

AC:

4696

AN:

10572

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.458

AC:

31145

AN:

68006

Other (OTH)

AF:

0.480

AC:

1011

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1927

3854

5782

7709

9636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.490

Hom.:

5681

Bravo

AF:

0.493

Asia WGS

AF:

0.304

AC:

1061

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 05, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Autosomal recessive ataxia, Beauce type

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Arthrogryposis multiplex congenita 3, myogenic type

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.43

(source)

DANN

Benign

0.66

PhyloP100

0.095

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000053

dbscSNV1_RF

Benign

0.0020

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over