Variant rs1873176 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.9651+47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,612,906 control chromosomes in the GnomAD database, including 225,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16787 hom., cov: 31)

Exomes 𝑓: 0.53 ( 208292 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.293

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=-0.8).

BP6

Variant 6-152369424-G-A is Benign according to our data. Variant chr6-152369424-G-A is described in ClinVar as [Benign]. Clinvar id is 262204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 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.9651+47C>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.9651+47C>T		intron_variant		1	NM_182961.4	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69323

AN:

151780

Hom.:

16784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.540

Gnomad EAS

AF:

0.457

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.471

GnomAD3 exomes

AF:

0.489

AC:

122392

AN:

250388

Hom.:

30877

AF XY:

0.491

AC XY:

66495

AN XY:

135430

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.553

Gnomad EAS exome

AF:

0.443

Gnomad SAS exome

AF:

0.421

Gnomad FIN exome

AF:

0.491

Gnomad NFE exome

AF:

0.539

Gnomad OTH exome

AF:

0.499

GnomAD4 exome

AF:

0.530

AC:

774860

AN:

1461008

Hom.:

208292

Cov.:

AF XY:

0.528

AC XY:

383418

AN XY:

726824

show subpopulations

Gnomad4 AFR exome

AF:

0.272

Gnomad4 AMR exome

AF:

0.489

Gnomad4 ASJ exome

AF:

0.551

Gnomad4 EAS exome

AF:

0.462

Gnomad4 SAS exome

AF:

0.423

Gnomad4 FIN exome

AF:

0.490

Gnomad4 NFE exome

AF:

0.554

Gnomad4 OTH exome

AF:

0.509

GnomAD4 genome

AF:

0.457

AC:

69343

AN:

151898

Hom.:

16787

Cov.:

AF XY:

0.454

AC XY:

33735

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.287

Gnomad4 AMR

AF:

0.500

Gnomad4 ASJ

AF:

0.540

Gnomad4 EAS

AF:

0.458

Gnomad4 SAS

AF:

0.435

Gnomad4 FIN

AF:

0.480

Gnomad4 NFE

AF:

0.542

Gnomad4 OTH

AF:

0.471

Alfa

AF:

0.479

Hom.:

4655

Bravo

AF:

0.450

Asia WGS

AF:

0.473

AC:

1649

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

-0.80

CADD

Benign

0.79

DANN

Benign

0.79

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