NM_182961.4:c.9808-50G>A

Variant names:

• chr6-152367432-C-T
• rs7775637
• NM_182961.4:c.9808-50G>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.9808-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 1,607,646 control chromosomes in the GnomAD database, including 663,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64219 hom., cov: 32)
  • Exomes 𝑓: 0.91 (599668 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.96

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 6-152367432-C-T is Benign according to our data. Variant chr6-152367432-C-T is described in ClinVar as [Benign]. Clinvar id is 262206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.9808-50G>A		intron_variant	Intron 61 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.9808-50G>A		intron_variant	Intron 61 of 145	1	NM_182961.4	ENSP00000356224.5

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139458 AN: 152158 Hom.: 64154 Cov.: 32

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.899

GnomAD3 exomes AF: 0.869 AC: 214568 AN: 246972 Hom.: 94233 AF XY: 0.867 AC XY: 116127 AN XY: 133920

Gnomad AFR exome AF: 0.966

Gnomad AMR exome AF: 0.746

Gnomad ASJ exome AF: 0.861

Gnomad EAS exome AF: 0.856

Gnomad SAS exome AF: 0.730

Gnomad FIN exome AF: 0.935

Gnomad NFE exome AF: 0.922

Gnomad OTH exome AF: 0.881

GnomAD4 exome AF: 0.906 AC: 1318425 AN: 1455370 Hom.: 599668 Cov.: 34 AF XY: 0.901 AC XY: 652889 AN XY: 724390

Gnomad4 AFR exome AF: 0.963

Gnomad4 AMR exome AF: 0.761

Gnomad4 ASJ exome AF: 0.860

Gnomad4 EAS exome AF: 0.888

Gnomad4 SAS exome AF: 0.733

Gnomad4 FIN exome AF: 0.931

Gnomad4 NFE exome AF: 0.925

Gnomad4 OTH exome AF: 0.895

GnomAD4 genome AF: 0.917 AC: 139585 AN: 152276 Hom.: 64219 Cov.: 32 AF XY: 0.912 AC XY: 67906 AN XY: 74466

Gnomad4 AFR AF: 0.964

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.936

Gnomad4 NFE AF: 0.923

Gnomad4 OTH AF: 0.900

Alfa AF: 0.915 Hom.: 23126

Bravo AF: 0.913

Asia WGS AF: 0.808 AC: 2812 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0010
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: rs7775637; hg19: chr6-152688567;