rs2813486

Positions:

• chr6-152145300-A-G
• chr6-152145300-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182961.4(SYNE1):​c.24977-1535T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 658,770 control chromosomes in the GnomAD database, including 41,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (10818 hom., cov: 33)
  • Exomes 𝑓: 0.34 (30688 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.822

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-152145300-A-G is Benign according to our data. Variant chr6-152145300-A-G is described in ClinVar as [Benign]. Clinvar id is 670215.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_001347702.2	c.1510+187T>C		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4	c.24977-1535T>C		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5	c.1510+187T>C		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10	c.24977-1535T>C		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56213 AN: 151724 Hom.: 10804 Cov.: 33

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.340 AC: 172454 AN: 506930 Hom.: 30688 Cov.: 5 AF XY: 0.344 AC XY: 93716 AN XY: 272094

Gnomad4 AFR exome AF: 0.443

Gnomad4 AMR exome AF: 0.490

Gnomad4 ASJ exome AF: 0.406

Gnomad4 EAS exome AF: 0.309

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.357

GnomAD4 genome AF: 0.371 AC: 56272 AN: 151840 Hom.: 10818 Cov.: 33 AF XY: 0.370 AC XY: 27501 AN XY: 74244

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.413

Alfa AF: 0.347 Hom.: 1116

Bravo AF: 0.395

Asia WGS AF: 0.373 AC: 1296 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.2
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2813486; hg19: chr6-152466435; COSMIC: COSV55114739; COSMIC: COSV55114739;