Variant rs56877632 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.8177+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,613,612 control chromosomes in the GnomAD database, including 3,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 2039 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 1887 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.64

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=-0.82).

BP6

Variant 6-152390271-G-A is Benign according to our data. Variant chr6-152390271-G-A is described in ClinVar as [Benign]. Clinvar id is 130450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152390271-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.8177+9C>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.8177+9C>T	intron_variant	1	NM_182961.4	P1	Q8NF91-1
SYNE1	ENST00000423061.6 linkuse as main transcript	c.8198+9C>T	intron_variant	1
SYNE1	ENST00000461872.6 linkuse as main transcript	n.8395+9C>T	intron_variant, non_coding_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.0886

AC:

13455

AN:

151930

Hom.:

2031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.0594

GnomAD3 exomes

AF:

0.0231

AC:

5811

AN:

251106

Hom.:

828

AF XY:

0.0170

AC XY:

2306

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.314

Gnomad AMR exome

AF:

0.0143

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.00931

AC:

13604

AN:

1461564

Hom.:

1887

Cov.:

AF XY:

0.00811

AC XY:

5897

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.319

Gnomad4 AMR exome

AF:

0.0170

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000754

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000633

Gnomad4 OTH exome

AF:

0.0219

GnomAD4 genome

AF:

0.0887

AC:

13494

AN:

152048

Hom.:

2039

Cov.:

AF XY:

0.0860

AC XY:

6394

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.308

Gnomad4 AMR

AF:

0.0342

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.0588

Alfa

AF:

0.0160

Hom.:

491

Bravo

AF:

0.102

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 16, 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	-	- -
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. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 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 12, 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 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.012

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