rs719764

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2476 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.23145+586C>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.23145+586C>T		intron_variant		1	NM_182961.4	P1

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

Gnomad4 AFR AF: 0.00408

Gnomad4 AMR AF: 0.00760

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00375

Gnomad4 FIN AF: 0.0735

Gnomad4 NFE AF: 0.0200

Gnomad4 OTH AF: 0.00711

Alfa AF: 0.0119 Hom.: 1144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.036
DANN	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs719764; hg19: chr6-152522373;