rs4523096

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1463+24G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,584,074 control chromosomes in the GnomAD database, including 422,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 48411 hom., cov: 31)

Exomes 𝑓: 0.72 ( 374293 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0790

Publications

14 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=-0.88).

BP6

Variant 6-152472277-C-A is Benign according to our data. Variant chr6-152472277-C-A is described in ClinVar as Benign. ClinVar VariationId is 262164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.1463+24G>T		intron_variant	Intron 15 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 link	c.1463+24G>T		intron_variant	Intron 15 of 145	1	NM_182961.4	ENSP00000356224.5		Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.790

AC:

120007

AN:

151966

Hom.:

48363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.943

Gnomad AMI

AF:

0.609

Gnomad AMR

AF:

0.731

Gnomad ASJ

AF:

0.738

Gnomad EAS

AF:

0.962

Gnomad SAS

AF:

0.790

Gnomad FIN

AF:

0.794

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.783

GnomAD2 exomes

AF:

0.759

AC:

189973

AN:

250272

AF XY:

0.758

show subpopulations

Gnomad AFR exome

AF:

0.948

Gnomad AMR exome

AF:

0.697

Gnomad ASJ exome

AF:

0.738

Gnomad EAS exome

AF:

0.966

Gnomad FIN exome

AF:

0.791

Gnomad NFE exome

AF:

0.707

Gnomad OTH exome

AF:

0.743

GnomAD4 exome

AF:

0.720

AC:

1031097

AN:

1431990

Hom.:

374293

Cov.:

AF XY:

0.722

AC XY:

515819

AN XY:

714424

show subpopulations

African (AFR)

AF:

0.954

AC:

31327

AN:

32850

American (AMR)

AF:

0.702

AC:

31289

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.737

AC:

19137

AN:

25958

East Asian (EAS)

AF:

0.979

AC:

38749

AN:

39566

South Asian (SAS)

AF:

0.784

AC:

66869

AN:

85284

European-Finnish (FIN)

AF:

0.785

AC:

41874

AN:

53368

Middle Eastern (MID)

AF:

0.786

AC:

4484

AN:

5706

European-Non Finnish (NFE)

AF:

0.694

AC:

752907

AN:

1085274

Other (OTH)

AF:

0.749

AC:

44461

AN:

59390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

14276

28553

42829

57106

71382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19048

38096

57144

76192

95240

<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:

0.790

AC:

120115

AN:

152084

Hom.:

48411

Cov.:

AF XY:

0.794

AC XY:

59010

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.943

AC:

39153

AN:

41524

American (AMR)

AF:

0.730

AC:

11154

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.738

AC:

2561

AN:

3472

East Asian (EAS)

AF:

0.963

AC:

4986

AN:

5180

South Asian (SAS)

AF:

0.790

AC:

3804

AN:

4816

European-Finnish (FIN)

AF:

0.794

AC:

8381

AN:

10560

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.701

AC:

47650

AN:

67948

Other (OTH)

AF:

0.781

AC:

1647

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1200

2400

3600

4800

6000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<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:

0.753

Hom.:

49001

Bravo

AF:

0.793

Asia WGS

AF:

0.867

AC:

3014

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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 14, 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. -

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

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

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

-0.88

CADD

Benign

0.20

(source)

DANN

Benign

0.60

PhyloP100

0.079

PromoterAI

-0.060

Neutral

(source)

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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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