Variant rs2141152 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.130-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,600,598 control chromosomes in the GnomAD database, including 84,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.27 ( 6476 hom., cov: 32)

Exomes 𝑓: 0.32 ( 77640 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.334

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-152526200-G-A is Benign according to our data. Variant chr6-152526200-G-A is described in ClinVar as [Benign]. Clinvar id is 262161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 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.130-25C>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.130-25C>T		intron_variant		1	NM_182961.4	ENSP00000356224.5		Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41182

AN:

151956

Hom.:

6477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.252

GnomAD3 exomes

AF:

0.294

AC:

73453

AN:

249680

Hom.:

12112

AF XY:

0.300

AC XY:

40430

AN XY:

134948

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.281

Gnomad EAS exome

AF:

0.447

Gnomad SAS exome

AF:

0.242

Gnomad FIN exome

AF:

0.462

Gnomad NFE exome

AF:

0.324

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.322

AC:

465901

AN:

1448524

Hom.:

77640

Cov.:

AF XY:

0.320

AC XY:

230913

AN XY:

721388

show subpopulations

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.277

Gnomad4 EAS exome

AF:

0.463

Gnomad4 SAS exome

AF:

0.245

Gnomad4 FIN exome

AF:

0.458

Gnomad4 NFE exome

AF:

0.331

Gnomad4 OTH exome

AF:

0.307

GnomAD4 genome

AF:

0.271

AC:

41189

AN:

152074

Hom.:

6476

Cov.:

AF XY:

0.278

AC XY:

20620

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.454

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.473

Gnomad4 NFE

AF:

0.326

Gnomad4 OTH

AF:

0.249

Alfa

AF:

0.307

Hom.:

5184

Bravo

AF:

0.246

Asia WGS

AF:

0.322

AC:

1119

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 26, 2018

- -

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

-0.77

CADD

Benign

0.77

DANN

Benign

0.71

BranchPoint Hunter

0.0

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