Variant rs4343926 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.1351-27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,561,490 control chromosomes in the GnomAD database, including 135,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 22009 hom., cov: 30)

Exomes 𝑓: 0.41 ( 113053 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.751

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 6-152472440-A-G is Benign according to our data. Variant chr6-152472440-A-G is described in ClinVar as [Benign]. Clinvar id is 262163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.1351-27T>C		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.1351-27T>C		intron_variant		1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78306

AN:

151308

Hom.:

21970

Cov.:

show subpopulations

Gnomad AFR

AF:

0.730

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.417

Gnomad ASJ

AF:

0.494

Gnomad EAS

AF:

0.755

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.383

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.417

Gnomad OTH

AF:

0.521

GnomAD3 exomes

AF:

0.441

AC:

104142

AN:

236384

Hom.:

23418

AF XY:

0.442

AC XY:

56416

AN XY:

127724

show subpopulations

Gnomad AFR exome

AF:

0.726

Gnomad AMR exome

AF:

0.301

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.720

Gnomad SAS exome

AF:

0.483

Gnomad FIN exome

AF:

0.378

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.413

AC:

581712

AN:

1410066

Hom.:

113053

Cov.:

AF XY:

0.416

AC XY:

292291

AN XY:

703332

show subpopulations

Gnomad4 AFR exome

AF:

0.715

Gnomad4 AMR exome

AF:

0.320

Gnomad4 ASJ exome

AF:

0.463

Gnomad4 EAS exome

AF:

0.714

Gnomad4 SAS exome

AF:

0.490

Gnomad4 FIN exome

AF:

0.381

Gnomad4 NFE exome

AF:

0.389

Gnomad4 OTH exome

AF:

0.443

GnomAD4 genome

AF:

0.518

AC:

78395

AN:

151424

Hom.:

22009

Cov.:

AF XY:

0.516

AC XY:

38183

AN XY:

73962

show subpopulations

Gnomad4 AFR

AF:

0.731

Gnomad4 AMR

AF:

0.417

Gnomad4 ASJ

AF:

0.494

Gnomad4 EAS

AF:

0.755

Gnomad4 SAS

AF:

0.538

Gnomad4 FIN

AF:

0.383

Gnomad4 NFE

AF:

0.417

Gnomad4 OTH

AF:

0.520

Alfa

AF:

0.446

Hom.:

5803

Bravo

AF:

0.531

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.66

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over