rs17082180

chr6-152136958-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182961.4(SYNE1):c.25459-140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 824,566 control chromosomes in the GnomAD database, including 8,112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1463 hom., cov: 32)
  • Exomes 𝑓: 0.13 (6649 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.276

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-152136958-G-A is Benign according to our data. Variant chr6-152136958-G-A is described in ClinVar as [Benign]. Clinvar id is 1295984.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_001347702.2	c.1993-140C>T		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4	c.25459-140C>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5	c.1993-140C>T		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10	c.25459-140C>T		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20539 AN: 151882 Hom.: 1450 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0708

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.135 AC: 90697 AN: 672566 Hom.: 6649 AF XY: 0.135 AC XY: 48047 AN XY: 356452

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.0542

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0892

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.136 AC: 20599 AN: 152000 Hom.: 1463 Cov.: 32 AF XY: 0.134 AC XY: 9956 AN XY: 74276

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0706

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0601

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.110

Alfa AF: 0.145 Hom.: 961

Bravo AF: 0.124

Asia WGS AF: 0.140 AC: 491 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.90
Cadd	Benign	2.4
Dann	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17082180; hg19: chr6-152458093; COSMIC: COSV55015762;