Variant rs2813486 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_182961.4(SYNE1):c.24977-1535T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 658,770 control chromosomes in the GnomAD database, including 41,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 10818 hom., cov: 33)

Exomes 𝑓: 0.34 ( 30688 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.822

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:

SYNE1 (HGNC:):

SYNE1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-152145300-A-G is Benign according to our data. Variant chr6-152145300-A-G is described in ClinVar as [Benign]. Clinvar id is 670215.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 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.24977-1535T>C		intron_variant		ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2 linkuse as main transcript	c.1510+187T>C		intron_variant		ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.24977-1535T>C		intron_variant		1	NM_182961.4	ENSP00000356224.5		Q8NF91-1
SYNE1	ENST00000354674.5 linkuse as main transcript	c.1510+187T>C		intron_variant		5	NM_001347702.2	ENSP00000346701.4		F8WAI0

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56213

AN:

151724

Hom.:

10804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.447

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.411

GnomAD4 exome

AF:

0.340

AC:

172454

AN:

506930

Hom.:

30688

Cov.:

AF XY:

0.344

AC XY:

93716

AN XY:

272094

show subpopulations

Gnomad4 AFR exome

AF:

0.443

Gnomad4 AMR exome

AF:

0.490

Gnomad4 ASJ exome

AF:

0.406

Gnomad4 EAS exome

AF:

0.309

Gnomad4 SAS exome

AF:

0.413

Gnomad4 FIN exome

AF:

0.217

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.371

AC:

56272

AN:

151840

Hom.:

10818

Cov.:

AF XY:

0.370

AC XY:

27501

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.446

Gnomad4 AMR

AF:

0.469

Gnomad4 ASJ

AF:

0.408

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.408

Gnomad4 FIN

AF:

0.215

Gnomad4 NFE

AF:

0.326

Gnomad4 OTH

AF:

0.413

Alfa

AF:

0.347

Hom.:

1116

Bravo

AF:

0.395

Asia WGS

AF:

0.373

AC:

1296

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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

-0.91

CADD

Benign

5.2

DANN

Benign

0.46

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