rs3818110

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.25458+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,610,822 control chromosomes in the GnomAD database, including 128,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14404 hom., cov: 31)

Exomes 𝑓: 0.39 ( 114285 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.287

Publications

7 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:

ENSG00000300811 (HGNC:):

ENSG00000300811 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=-0.9).

BP6

Variant 6-152139926-G-A is Benign according to our data. Variant chr6-152139926-G-A is described in ClinVar as [Benign]. Clinvar id is 262193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.25458+24C>T		intron_variant	Intron 140 of 145	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2 link	c.1992+24C>T		intron_variant	Intron 12 of 17	ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 link	c.25458+24C>T		intron_variant	Intron 140 of 145	1	NM_182961.4	ENSP00000356224.5		Q8NF91-1
SYNE1	ENST00000354674.5 link	c.1992+24C>T		intron_variant	Intron 12 of 17	5	NM_001347702.2	ENSP00000346701.4		F8WAI0

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

64863

AN:

151290

Hom.:

14403

Cov.:

show subpopulations

Gnomad AFR

AF:

0.526

Gnomad AMI

AF:

0.362

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.468

GnomAD2 exomes

AF:

0.408

AC:

101697

AN:

249532

AF XY:

0.404

show subpopulations

Gnomad AFR exome

AF:

0.529

Gnomad AMR exome

AF:

0.532

Gnomad ASJ exome

AF:

0.504

Gnomad EAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.248

Gnomad NFE exome

AF:

0.379

Gnomad OTH exome

AF:

0.423

GnomAD4 exome

AF:

0.392

AC:

571844

AN:

1459412

Hom.:

114285

Cov.:

AF XY:

0.393

AC XY:

285575

AN XY:

726014

show subpopulations

African (AFR)

AF:

0.524

AC:

17524

AN:

33416

American (AMR)

AF:

0.532

AC:

23769

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

13299

AN:

26128

East Asian (EAS)

AF:

0.308

AC:

12240

AN:

39684

South Asian (SAS)

AF:

0.450

AC:

38745

AN:

86148

European-Finnish (FIN)

AF:

0.249

AC:

13300

AN:

53356

Middle Eastern (MID)

AF:

0.489

AC:

2206

AN:

4514

European-Non Finnish (NFE)

AF:

0.384

AC:

426272

AN:

1111318

Other (OTH)

AF:

0.407

AC:

24489

AN:

60198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

19760

39520

59279

79039

98799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.429

AC:

64914

AN:

151410

Hom.:

14404

Cov.:

AF XY:

0.425

AC XY:

31449

AN XY:

74000

show subpopulations

African (AFR)

AF:

0.525

AC:

21663

AN:

41244

American (AMR)

AF:

0.498

AC:

7588

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

1739

AN:

3468

East Asian (EAS)

AF:

0.309

AC:

1579

AN:

5110

South Asian (SAS)

AF:

0.437

AC:

2093

AN:

4788

European-Finnish (FIN)

AF:

0.245

AC:

2581

AN:

10542

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26224

AN:

67738

Other (OTH)

AF:

0.467

AC:

980

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1763

3527

5290

7054

8817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.402

Hom.:

5978

Bravo

AF:

0.458

Asia WGS

AF:

0.363

AC:

1260

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 18, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.0

(source)

DANN

Benign

0.90

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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rs3818110

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