rs2295193

Variant names:

• chr6-152131959-G-A
• rs2295193
• NM_182961.4:c.26094+163C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive ataxia, Beauce type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• arthrogryposis multiplex congenita 3, myogenic type

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
• autosomal dominant Emery-Dreifuss muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive myogenic arthrogryposis multiplex congenita

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000300811 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.26094+163C>T		intron_variant	Intron 144 of 145	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2	c.2628+163C>T		intron_variant	Intron 16 of 17	ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.26094+163C>T		intron_variant	Intron 144 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000354674.5	c.2628+163C>T		intron_variant	Intron 16 of 17	5	NM_001347702.2	ENSP00000346701.4

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

African (AFR) AF: 0.714 AC: 29575 AN: 41434

American (AMR) AF: 0.645 AC: 9843 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1957 AN: 3466

East Asian (EAS) AF: 0.737 AC: 3794 AN: 5150

South Asian (SAS) AF: 0.727 AC: 3503 AN: 4818

European-Finnish (FIN) AF: 0.526 AC: 5551 AN: 10546

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36736 AN: 67972

Other (OTH) AF: 0.612 AC: 1293 AN: 2114

Alfa AF: 0.568 Hom.: 108799

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

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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