rs4523096

Positions:

• chr6-152472277-C-A
• chr6-152472277-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182961.4(SYNE1):​c.1463+24G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,584,074 control chromosomes in the GnomAD database, including 422,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (48411 hom., cov: 31)
  • Exomes 𝑓: 0.72 (374293 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0790

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-152472277-C-A is Benign according to our data. Variant chr6-152472277-C-A is described in ClinVar as [Benign]. Clinvar id is 262164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.1463+24G>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.1463+24G>T		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120007 AN: 151966 Hom.: 48363 Cov.: 31

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.783

GnomAD3 exomes AF: 0.759 AC: 189973 AN: 250272 Hom.: 73156 AF XY: 0.758 AC XY: 102462 AN XY: 135218

Gnomad AFR exome AF: 0.948

Gnomad AMR exome AF: 0.697

Gnomad ASJ exome AF: 0.738

Gnomad EAS exome AF: 0.966

Gnomad SAS exome AF: 0.784

Gnomad FIN exome AF: 0.791

Gnomad NFE exome AF: 0.707

Gnomad OTH exome AF: 0.743

GnomAD4 exome AF: 0.720 AC: 1031097 AN: 1431990 Hom.: 374293 Cov.: 25 AF XY: 0.722 AC XY: 515819 AN XY: 714424

Gnomad4 AFR exome AF: 0.954

Gnomad4 AMR exome AF: 0.702

Gnomad4 ASJ exome AF: 0.737

Gnomad4 EAS exome AF: 0.979

Gnomad4 SAS exome AF: 0.784

Gnomad4 FIN exome AF: 0.785

Gnomad4 NFE exome AF: 0.694

Gnomad4 OTH exome AF: 0.749

GnomAD4 genome AF: 0.790 AC: 120115 AN: 152084 Hom.: 48411 Cov.: 31 AF XY: 0.794 AC XY: 59010 AN XY: 74346

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.781

Alfa AF: 0.743 Hom.: 13952

Bravo AF: 0.793

Asia WGS AF: 0.867 AC: 3014 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

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	-0.88
CADD	Benign	0.20
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4523096; hg19: chr6-152793412;