rs9478310

chr6-152282004-T-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.18208-24A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 1,610,520 control chromosomes in the GnomAD database, including 3,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (421 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3574 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.50

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=-0.9).
• BP6: Variant 6-152282004-T-C is Benign according to our data. Variant chr6-152282004-T-C is described in ClinVar as [Benign]. Clinvar id is 262174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152282004-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.18208-24A>G		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.18208-24A>G		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10519 AN: 152128 Hom.: 421 Cov.: 32

Gnomad AFR AF: 0.0873

Gnomad AMI AF: 0.0980

Gnomad AMR AF: 0.0514

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0550

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0774

GnomAD3 exomes AF: 0.0671 AC: 16449 AN: 245092 Hom.: 692 AF XY: 0.0707 AC XY: 9392 AN XY: 132916

Gnomad AFR exome AF: 0.0879

Gnomad AMR exome AF: 0.0362

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.0602

Gnomad SAS exome AF: 0.116

Gnomad FIN exome AF: 0.0282

Gnomad NFE exome AF: 0.0639

Gnomad OTH exome AF: 0.0763

GnomAD4 exome AF: 0.0660 AC: 96315 AN: 1458274 Hom.: 3574 Cov.: 30 AF XY: 0.0683 AC XY: 49578 AN XY: 725612

Gnomad4 AFR exome AF: 0.0868

Gnomad4 AMR exome AF: 0.0384

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.0479

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0313

Gnomad4 NFE exome AF: 0.0626

Gnomad4 OTH exome AF: 0.0778

GnomAD4 genome AF: 0.0692 AC: 10530 AN: 152246 Hom.: 421 Cov.: 32 AF XY: 0.0686 AC XY: 5109 AN XY: 74462

Gnomad4 AFR AF: 0.0872

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0553

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0296

Gnomad4 NFE AF: 0.0633

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0757 Hom.: 148

Bravo AF: 0.0720

Asia WGS AF: 0.0980 AC: 341 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

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.41
La Branchor		0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9478310; hg19: chr6-152603139; COSMIC: COSV54939256; COSMIC: COSV54939256;