rs1744380

Positions:

• chr6-152621686-G-A
• chr6-152621686-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182961.4(SYNE1):​c.67+6579C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 151,216 control chromosomes in the GnomAD database, including 38,365 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 0.71 (38365 hom., cov: 31)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.67+6579C>T		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.67+6579C>T		intron_variant		1	NM_182961.4	ENSP00000356224	P1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 107615 AN: 151098 Hom.: 38355 Cov.: 31

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.712 AC: 107671 AN: 151216 Hom.: 38365 Cov.: 31 AF XY: 0.707 AC XY: 52211 AN XY: 73844

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.729

Alfa AF: 0.703 Hom.: 7079

Bravo AF: 0.720

Asia WGS AF: 0.698 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.094
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1744380; hg19: chr6-152942821;