rs9371243

chr6-152218215-C-G

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.22191+42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,608,724 control chromosomes in the GnomAD database, including 47,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4014 hom., cov: 30)
  • Exomes 𝑓: 0.23 (43843 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.674

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=-0.87).
• BP6: Variant 6-152218215-C-G is Benign according to our data. Variant chr6-152218215-C-G is described in ClinVar as [Benign]. Clinvar id is 262183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.22191+42G>C		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.22191+42G>C		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31958 AN: 151654 Hom.: 4012 Cov.: 30

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.265 AC: 66404 AN: 250676 Hom.: 10355 AF XY: 0.267 AC XY: 36134 AN XY: 135474

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.271

Gnomad EAS exome AF: 0.571

Gnomad SAS exome AF: 0.319

Gnomad FIN exome AF: 0.345

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.235 AC: 342126 AN: 1456952 Hom.: 43843 Cov.: 33 AF XY: 0.236 AC XY: 171261 AN XY: 725080

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.526

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.211 AC: 31976 AN: 151772 Hom.: 4014 Cov.: 30 AF XY: 0.221 AC XY: 16345 AN XY: 74116

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.186

Alfa AF: 0.213 Hom.: 677

Bravo AF: 0.197

Asia WGS AF: 0.406 AC: 1413 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

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 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.021
Dann	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9371243; hg19: chr6-152539350; COSMIC: COSV54896874;