Variant 6-152391617-C-T 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.7713-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,482,530 control chromosomes in the GnomAD database, including 126,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18598 hom., cov: 27)

Exomes 𝑓: 0.39 ( 107777 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.471

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=-0.89).

BP6

Variant 6-152391617-C-T is Benign according to our data. Variant chr6-152391617-C-T is described in ClinVar as [Benign]. Clinvar id is 262200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.7713-49G>A		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.7713-49G>A	intron_variant	1	NM_182961.4	P1	Q8NF91-1
SYNE1	ENST00000423061.6 linkuse as main transcript	c.7734-49G>A	intron_variant	1
SYNE1	ENST00000461872.6 linkuse as main transcript	n.7931-49G>A	intron_variant, non_coding_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

70838

AN:

149384

Hom.:

18577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.684

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.752

Gnomad SAS

AF:

0.501

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.510

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.461

GnomAD3 exomes

AF:

0.368

AC:

44660

AN:

121384

Hom.:

10525

AF XY:

0.368

AC XY:

24403

AN XY:

66240

show subpopulations

Gnomad AFR exome

AF:

0.668

Gnomad AMR exome

AF:

0.245

Gnomad ASJ exome

AF:

0.308

Gnomad EAS exome

AF:

0.747

Gnomad SAS exome

AF:

0.424

Gnomad FIN exome

AF:

0.278

Gnomad NFE exome

AF:

0.314

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.385

AC:

513482

AN:

1333032

Hom.:

107777

Cov.:

AF XY:

0.386

AC XY:

254023

AN XY:

657354

show subpopulations

Gnomad4 AFR exome

AF:

0.691

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.346

Gnomad4 EAS exome

AF:

0.771

Gnomad4 SAS exome

AF:

0.463

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.417

GnomAD4 genome

AF:

0.474

AC:

70907

AN:

149498

Hom.:

18598

Cov.:

AF XY:

0.474

AC XY:

34504

AN XY:

72726

show subpopulations

Gnomad4 AFR

AF:

0.684

Gnomad4 AMR

AF:

0.359

Gnomad4 ASJ

AF:

0.380

Gnomad4 EAS

AF:

0.752

Gnomad4 SAS

AF:

0.500

Gnomad4 FIN

AF:

0.365

Gnomad4 NFE

AF:

0.376

Gnomad4 OTH

AF:

0.461

Alfa

AF:

0.337

Hom.:

2319

Bravo

AF:

0.485

Asia WGS

AF:

0.598

AC:

2081

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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. -

Arthrogryposis multiplex congenita 3, myogenic type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.5

DANN

Benign

0.56

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