Variant chr6-152462940-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.2098-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,600,770 control chromosomes in the GnomAD database, including 19,630 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3054 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16576 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.31

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 6-152462940-C-T is Benign according to our data. Variant chr6-152462940-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 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.2098-50G>A		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.2098-50G>A		intron_variant		1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27356

AN:

151848

Hom.:

3057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.159

AC:

39480

AN:

247682

Hom.:

4264

AF XY:

0.160

AC XY:

21443

AN XY:

134142

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.0747

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.426

Gnomad SAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.137

AC:

198919

AN:

1448802

Hom.:

16576

Cov.:

AF XY:

0.139

AC XY:

100114

AN XY:

721626

show subpopulations

Gnomad4 AFR exome

AF:

0.287

Gnomad4 AMR exome

AF:

0.0794

Gnomad4 ASJ exome

AF:

0.146

Gnomad4 EAS exome

AF:

0.426

Gnomad4 SAS exome

AF:

0.190

Gnomad4 FIN exome

AF:

0.157

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.180

AC:

27376

AN:

151968

Hom.:

3054

Cov.:

AF XY:

0.184

AC XY:

13641

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.429

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.165

Alfa

AF:

0.147

Hom.:

543

Bravo

AF:

0.182

Asia WGS

AF:

0.291

AC:

1010

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.5

DANN

Benign

0.55

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