Variant rs1538 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 ENST00000367255.10(SYNE1):c.16711-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,608,712 control chromosomes in the GnomAD database, including 1,185 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 0.027 ( 106 hom., cov: 32)

Exomes 𝑓: 0.030 ( 1079 hom. )

Consequence

SYNE1
ENST00000367255.10 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.959

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

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 6-152310898-G-A is Benign according to our data. Variant chr6-152310898-G-A is described in ClinVar as [Benign]. Clinvar id is 262170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.127 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.16711-25C>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.16711-25C>T		intron_variant		1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.0273

AC:

4160

AN:

152114

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0269

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.0265

Gnomad FIN

AF:

0.0422

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0274

Gnomad OTH

AF:

0.0205

GnomAD3 exomes

AF:

0.0369

AC:

9035

AN:

244862

Hom.:

342

AF XY:

0.0354

AC XY:

4680

AN XY:

132262

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.0460

Gnomad ASJ exome

AF:

0.00484

Gnomad EAS exome

AF:

0.148

Gnomad SAS exome

AF:

0.0201

Gnomad FIN exome

AF:

0.0429

Gnomad NFE exome

AF:

0.0257

Gnomad OTH exome

AF:

0.0339

GnomAD4 exome

AF:

0.0304

AC:

44345

AN:

1456480

Hom.:

1079

Cov.:

AF XY:

0.0297

AC XY:

21553

AN XY:

724494

show subpopulations

Gnomad4 AFR exome

AF:

0.0107

Gnomad4 AMR exome

AF:

0.0449

Gnomad4 ASJ exome

AF:

0.00484

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.0178

Gnomad4 FIN exome

AF:

0.0425

Gnomad4 NFE exome

AF:

0.0273

Gnomad4 OTH exome

AF:

0.0304

GnomAD4 genome

AF:

0.0273

AC:

4162

AN:

152232

Hom.:

106

Cov.:

AF XY:

0.0282

AC XY:

2097

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0132

Gnomad4 AMR

AF:

0.0269

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.135

Gnomad4 SAS

AF:

0.0263

Gnomad4 FIN

AF:

0.0422

Gnomad4 NFE

AF:

0.0274

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0244

Hom.:

Bravo

AF:

0.0269

Asia WGS

AF:

0.0790

AC:

272

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.8

DANN

Benign

0.68

BranchPoint Hunter

2.0

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