6-152146308-A-G

Position:

• chr6-152146308-A-G

Variant summary

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

The NM_182961.4(SYNE1):​c.24976+1737T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,096 control chromosomes in the GnomAD database, including 8,887 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 0.34 (8887 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_001347702.2	c.1442-753T>C		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4	c.24976+1737T>C		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5	c.1442-753T>C		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10	c.24976+1737T>C		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51229 AN: 151968 Hom.: 8881 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 AFR exome AF: 0.250

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.337 AC: 51270 AN: 152086 Hom.: 8887 Cov.: 32 AF XY: 0.338 AC XY: 25117 AN XY: 74348

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.385

Alfa AF: 0.348 Hom.: 3206

Bravo AF: 0.357

Asia WGS AF: 0.345 AC: 1196 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2673790; hg19: chr6-152467443; COSMIC: COSV54938444; COSMIC: COSV54938444;