rs7776344

Variant names:

• chr6-152462940-C-T
• rs7776344
• NM_182961.4:c.2098-50G>A

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.2098-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,600,770 control chromosomes in the GnomAD database, including 19,630 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 (3054 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16576 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.31

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=-0.8).
• BP6: Variant 6-152462940-C-T is Benign according to our data. Variant chr6-152462940-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262181.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 rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.2098-50G>A		intron_variant	Intron 19 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.2098-50G>A		intron_variant	Intron 19 of 145	1	NM_182961.4	ENSP00000356224.5

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27356 AN: 151848 Hom.: 3057 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: 39480 AN: 247682 Hom.: 4264 AF XY: 0.160 AC XY: 21443 AN XY: 134142

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.0747

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: 0.137 AC: 198919 AN: 1448802 Hom.: 16576 Cov.: 29 AF XY: 0.139 AC XY: 100114 AN XY: 721626

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: 0.190

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.180 AC: 27376 AN: 151968 Hom.: 3054 Cov.: 32 AF XY: 0.184 AC XY: 13641 AN XY: 74256

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.119

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: 0.165

Alfa AF: 0.147 Hom.: 543

Bravo AF: 0.182

Asia WGS AF: 0.291 AC: 1010 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7776344; hg19: chr6-152784075;