rs2813566

Positions:

• chr6-152136939-G-A

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.25459-121C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,065,856 control chromosomes in the GnomAD database, including 47,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7550 hom., cov: 32)
  • Exomes 𝑓: 0.29 (39970 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.163

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=-0.88).
• BP6: Variant 6-152136939-G-A is Benign according to our data. Variant chr6-152136939-G-A is described in ClinVar as [Benign]. Clinvar id is 670219.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_001347702.2	c.1993-121C>T		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4	c.25459-121C>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5	c.1993-121C>T		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10	c.25459-121C>T		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47148 AN: 151970 Hom.: 7554 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.287 AC: 262131 AN: 913768 Hom.: 39970 AF XY: 0.291 AC XY: 137085 AN XY: 471144

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.450

Gnomad4 ASJ exome AF: 0.346

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.298

GnomAD4 genome AF: 0.310 AC: 47182 AN: 152088 Hom.: 7550 Cov.: 32 AF XY: 0.311 AC XY: 23137 AN XY: 74360

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.342

Alfa AF: 0.294 Hom.: 3172

Bravo AF: 0.331

Asia WGS AF: 0.339 AC: 1175 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	-0.88
CADD	Benign	0.73
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2813566; hg19: chr6-152458074; COSMIC: COSV55082848;