rs34891041

Positions:

chr6-152213633-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_182961.4(SYNE1):c.22473G>A(p.Leu7491=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 1,613,978 control chromosomes in the GnomAD database, including 781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 91 hom., cov: 32)

Exomes 𝑓: 0.028 ( 690 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.417

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 6-152213633-C-T is Benign according to our data. Variant chr6-152213633-C-T is described in ClinVar as [Benign]. Clinvar id is 130421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152213633-C-T is described in Lovd as [Benign]. Variant chr6-152213633-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.417 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.031 (4722/152214) while in subpopulation AFR AF= 0.047 (1952/41538). AF 95% confidence interval is 0.0453. There are 91 homozygotes in gnomad4. There are 2222 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4722 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.22473G>A	p.Leu7491=	synonymous_variant	123/146	ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.22473G>A	p.Leu7491=	synonymous_variant	123/146	1	NM_182961.4	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.0310

AC:

4710

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0470

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.00927

Gnomad SAS

AF:

0.00415

Gnomad FIN

AF:

0.0332

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.0297

GnomAD3 exomes

AF:

0.0241

AC:

6055

AN:

251424

Hom.:

103

AF XY:

0.0229

AC XY:

3117

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.0471

Gnomad AMR exome

AF:

0.00945

Gnomad ASJ exome

AF:

0.0120

Gnomad EAS exome

AF:

0.00701

Gnomad SAS exome

AF:

0.00683

Gnomad FIN exome

AF:

0.0339

Gnomad NFE exome

AF:

0.0318

Gnomad OTH exome

AF:

0.0253

GnomAD4 exome

AF:

0.0280

AC:

40858

AN:

1461764

Hom.:

690

Cov.:

AF XY:

0.0271

AC XY:

19715

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0482

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.00824

Gnomad4 SAS exome

AF:

0.00677

Gnomad4 FIN exome

AF:

0.0351

Gnomad4 NFE exome

AF:

0.0307

Gnomad4 OTH exome

AF:

0.0258

GnomAD4 genome

AF:

0.0310

AC:

4722

AN:

152214

Hom.:

Cov.:

AF XY:

0.0299

AC XY:

2222

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0470

Gnomad4 AMR

AF:

0.0180

Gnomad4 ASJ

AF:

0.0136

Gnomad4 EAS

AF:

0.00929

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.0332

Gnomad4 NFE

AF:

0.0287

Gnomad4 OTH

AF:

0.0322

Alfa

AF:

0.0305

Hom.:

Bravo

AF:

0.0308

Asia WGS

AF:

0.0290

AC:

100

AN:

3478

EpiCase

AF:

0.0266

EpiControl

AF:

0.0260

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 28, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Dec 18, 2018

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

5.2

DANN

Benign

0.78

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