rs7747960

Positions:

• chr6-152470339-C-A

Variant summary

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

The NM_182961.4(SYNE1):​c.1632+1258G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,066 control chromosomes in the GnomAD database, including 3,065 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 0.18 (3065 hom., cov: 32)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.1632+1258G>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.1632+1258G>T		intron_variant		1	NM_182961.4	ENSP00000356224	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27455 AN: 151946 Hom.: 3068 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.181 AC: 27480 AN: 152066 Hom.: 3065 Cov.: 32 AF XY: 0.184 AC XY: 13708 AN XY: 74348

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.167

Alfa AF: 0.138 Hom.: 2181

Bravo AF: 0.183

Asia WGS AF: 0.293 AC: 1019 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7747960; hg19: chr6-152791474;