rs7775181

chr6-152462919-G-Achr6-152462919-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182961.4(SYNE1):c.2098-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,612,170 control chromosomes in the GnomAD database, including 19,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3049 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16739 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.650

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-152462919-G-A is Benign according to our data. Variant chr6-152462919-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.2098-29C>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.2098-29C>T		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27363 AN: 151858 Hom.: 3053 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.159 AC: 39769 AN: 249602 Hom.: 4305 AF XY: 0.160 AC XY: 21573 AN XY: 134980

Gnomad AFR exome AF: 0.284

Gnomad AMR exome AF: 0.0748

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.426

Gnomad SAS exome AF: 0.189

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.138 AC: 200821 AN: 1460196 Hom.: 16739 Cov.: 32 AF XY: 0.139 AC XY: 100910 AN XY: 726466

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.0794

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.426

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.180 AC: 27384 AN: 151974 Hom.: 3049 Cov.: 32 AF XY: 0.184 AC XY: 13636 AN XY: 74240

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.166

Alfa AF: 0.0960 Hom.: 191

Bravo AF: 0.182

Asia WGS AF: 0.293 AC: 1018 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

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	-0.89
Cadd	Benign	5.8
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7775181; hg19: chr6-152784054; COSMIC: COSV54993287; COSMIC: COSV54993287;