rs2747665

chr6-152147308-T-C

Variant summary

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

The NM_182961.4(SYNE1):c.24976+737A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,074 control chromosomes in the GnomAD database, including 11,037 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 0.37 (11032 hom., cov: 32)
  • Exomes 𝑓: 0.31 (5 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_001347702.2	c.1441+737A>G		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4	c.24976+737A>G		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5	c.1441+737A>G		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10	c.24976+737A>G		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56601 AN: 151882 Hom.: 11018 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.413

GnomAD4 exome AF: 0.311 AC: 23 AN: 74 Hom.: 5 Cov.: 0 AF XY: 0.290 AC XY: 18 AN XY: 62

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.373 AC: 56661 AN: 152000 Hom.: 11032 Cov.: 32 AF XY: 0.373 AC XY: 27681 AN XY: 74302

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.411

Alfa AF: 0.366 Hom.: 1593

Bravo AF: 0.397

Asia WGS AF: 0.353 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.6
Dann	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2747665; hg19: chr6-152468443; COSMIC: COSV54938458; COSMIC: COSV54938458;