Variant 6-152401093-A-G 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.7029+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,581,814 control chromosomes in the GnomAD database, including 131,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15834 hom., cov: 32)

Exomes 𝑓: 0.39 ( 115919 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00200

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

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 6-152401093-A-G is Benign according to our data. Variant chr6-152401093-A-G is described in ClinVar as [Benign]. Clinvar id is 262198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 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.7029+45T>C		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.7029+45T>C	intron_variant	1	NM_182961.4	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6 linkuse as main transcript	c.7050+45T>C	intron_variant	1		ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000461872.6 linkuse as main transcript	n.7247+45T>C	intron_variant	1

Frequencies

GnomAD3 genomes

AF:

0.443

AC:

67323

AN:

151936

Hom.:

15820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.564

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.354

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.756

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.437

GnomAD3 exomes

AF:

0.423

AC:

104729

AN:

247766

Hom.:

23921

AF XY:

0.425

AC XY:

57033

AN XY:

134046

show subpopulations

Gnomad AFR exome

AF:

0.567

Gnomad AMR exome

AF:

0.293

Gnomad ASJ exome

AF:

0.363

Gnomad EAS exome

AF:

0.767

Gnomad SAS exome

AF:

0.483

Gnomad FIN exome

AF:

0.393

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.393

AC:

562513

AN:

1429760

Hom.:

115919

Cov.:

AF XY:

0.397

AC XY:

282898

AN XY:

713442

show subpopulations

Gnomad4 AFR exome

AF:

0.564

Gnomad4 AMR exome

AF:

0.303

Gnomad4 ASJ exome

AF:

0.363

Gnomad4 EAS exome

AF:

0.776

Gnomad4 SAS exome

AF:

0.485

Gnomad4 FIN exome

AF:

0.390

Gnomad4 NFE exome

AF:

0.370

Gnomad4 OTH exome

AF:

0.418

GnomAD4 genome

AF:

0.443

AC:

67385

AN:

152054

Hom.:

15834

Cov.:

AF XY:

0.446

AC XY:

33128

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.564

Gnomad4 AMR

AF:

0.354

Gnomad4 ASJ

AF:

0.381

Gnomad4 EAS

AF:

0.757

Gnomad4 SAS

AF:

0.504

Gnomad4 FIN

AF:

0.382

Gnomad4 NFE

AF:

0.376

Gnomad4 OTH

AF:

0.436

Alfa

AF:

0.414

Hom.:

3821

Bravo

AF:

0.445

Asia WGS

AF:

0.587

AC:

2042

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

-0.84

CADD

Benign

1.8

DANN

Benign

0.50

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