rs2295193

Positions:

• chr6-152131959-G-A
• chr6-152131959-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182961.4(SYNE1):​c.26094+163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,972 control chromosomes in the GnomAD database, including 28,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (28917 hom., cov: 32)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.195

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-152131959-G-A is Benign according to our data. Variant chr6-152131959-G-A is described in ClinVar as [Benign]. Clinvar id is 670223.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_001347702.2	c.2628+163C>T		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4	c.26094+163C>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5	c.2628+163C>T		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10	c.26094+163C>T		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92780 AN: 151854 Hom.: 28883 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.611

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.611 AC: 92878 AN: 151972 Hom.: 28917 Cov.: 32 AF XY: 0.615 AC XY: 45655 AN XY: 74258

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.612

Alfa AF: 0.556 Hom.: 47258

Bravo AF: 0.621

Asia WGS AF: 0.712 AC: 2477 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.83
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2295193; hg19: chr6-152453094; COSMIC: COSV54922308; COSMIC: COSV54922308;