Variant rs4523096 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.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

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=-0.88).

BP6

Variant 6-152472277-C-A is Benign according to our data. Variant chr6-152472277-C-A is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.1463+24G>T		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.1463+24G>T		intron_variant		1	NM_182961.4	ENSP00000356224	P1	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

GnomAD3 exomes

AF:

0.759

AC:

189973

AN:

250272

Hom.:

73156

AF XY:

0.758

AC XY:

102462

AN XY:

135218

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 SAS exome

AF:

0.784

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

Gnomad4 AFR exome

AF:

0.954

Gnomad4 AMR exome

AF:

0.702

Gnomad4 ASJ exome

AF:

0.737

Gnomad4 EAS exome

AF:

0.979

Gnomad4 SAS exome

AF:

0.784

Gnomad4 FIN exome

AF:

0.785

Gnomad4 NFE exome

AF:

0.694

Gnomad4 OTH exome

AF:

0.749

GnomAD4 genome

AF:

0.790

AC:

120115

AN:

152084

Hom.:

48411

Cov.:

AF XY:

0.794

AC XY:

59010

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.943

Gnomad4 AMR

AF:

0.730

Gnomad4 ASJ

AF:

0.738

Gnomad4 EAS

AF:

0.963

Gnomad4 SAS

AF:

0.790

Gnomad4 FIN

AF:

0.794

Gnomad4 NFE

AF:

0.701

Gnomad4 OTH

AF:

0.781

Alfa

AF:

0.743

Hom.:

13952

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

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

-0.88

CADD

Benign

0.20

DANN

Benign

0.60

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