rs2252837

chr6-152147685-C-T

Variant summary

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

The NM_182961.4(SYNE1):c.24976+360G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 288,244 control chromosomes in the GnomAD database, including 16,481 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 0.36 (10304 hom., cov: 32)
  • Exomes 𝑓: 0.29 (6177 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_001347702.2	c.1441+360G>A		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4	c.24976+360G>A		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5	c.1441+360G>A		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10	c.24976+360G>A		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54921 AN: 151764 Hom.: 10290 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.292 AC: 39755 AN: 136362 Hom.: 6177 Cov.: 0 AF XY: 0.300 AC XY: 22214 AN XY: 74032

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.427

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.236

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.362 AC: 54983 AN: 151882 Hom.: 10304 Cov.: 32 AF XY: 0.363 AC XY: 26913 AN XY: 74208

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.401

Alfa AF: 0.342 Hom.: 1078

Bravo AF: 0.384

Asia WGS AF: 0.338 AC: 1175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.70
Dann	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2252837; hg19: chr6-152468820; COSMIC: COSV54938469; COSMIC: COSV54938469;