rs719764

Variant names:

• chr6-152201238-G-A
• rs719764
• NM_182961.4:c.23145+586C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152201238-G-A
• chr6-152201238-G-C
• chr6-152201238-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_182961.4(SYNE1):​c.23145+586C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 151,952 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.016 (54 hom., cov: 31)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0163 (2476/151952) while in subpopulation NFE AF = 0.02 (1358/67958). AF 95% confidence interval is 0.0191. There are 54 homozygotes in GnomAd4. There are 1327 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 54 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	NM_182961.4	MANE Select	c.23145+586C>T		intron	N/A	NP_892006.3
	SYNE1	NM_033071.5		c.22932+586C>T		intron	N/A	NP_149062.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.23145+586C>T		intron	N/A	ENSP00000356224.5
	SYNE1	ENST00000423061.6	TSL:1	c.22932+586C>T		intron	N/A	ENSP00000396024.1
	SYNE1	ENST00000367251.7	TSL:1	c.1911+586C>T		intron	N/A	ENSP00000356220.3

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2476 AN: 151834 Hom.: 54 Cov.: 31

Gnomad AFR AF: 0.00409

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00767

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00354

Gnomad FIN AF: 0.0735

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0200

Gnomad OTH AF: 0.00718

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

GnomAD4 genome AF: 0.0163 AC: 2476 AN: 151952 Hom.: 54 Cov.: 31 AF XY: 0.0179 AC XY: 1327 AN XY: 74244

African (AFR) AF: 0.00408 AC: 169 AN: 41438

American (AMR) AF: 0.00760 AC: 116 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00375 AC: 18 AN: 4804

European-Finnish (FIN) AF: 0.0735 AC: 775 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0200 AC: 1358 AN: 67958

Other (OTH) AF: 0.00711 AC: 15 AN: 2110

Alfa AF: 0.0119 Hom.: 1144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.036
DANN	Benign	0.90
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs719764; hg19: chr6-152522373;