rs17082389

chr6-152256617-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.19104+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 1,612,740 control chromosomes in the GnomAD database, including 3,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (319 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3597 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.41

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=-0.91).
• BP6: Variant 6-152256617-T-C is Benign according to our data. Variant chr6-152256617-T-C is described in ClinVar as [Benign]. Clinvar id is 262175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152256617-T-C is described in Lovd as [Benign]. Variant chr6-152256617-T-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.19104+17A>G		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.19104+17A>G		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9214 AN: 152080 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.0717

GnomAD3 exomes AF: 0.0680 AC: 17087 AN: 251346 Hom.: 756 AF XY: 0.0723 AC XY: 9816 AN XY: 135848

Gnomad AFR exome AF: 0.0610

Gnomad AMR exome AF: 0.0331

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.122

Gnomad SAS exome AF: 0.127

Gnomad FIN exome AF: 0.0218

Gnomad NFE exome AF: 0.0595

Gnomad OTH exome AF: 0.0761

GnomAD4 exome AF: 0.0647 AC: 94476 AN: 1460542 Hom.: 3597 Cov.: 31 AF XY: 0.0671 AC XY: 48777 AN XY: 726554

Gnomad4 AFR exome AF: 0.0591

Gnomad4 AMR exome AF: 0.0356

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.0226

Gnomad4 NFE exome AF: 0.0585

Gnomad4 OTH exome AF: 0.0761

GnomAD4 genome AF: 0.0606 AC: 9220 AN: 152198 Hom.: 319 Cov.: 32 AF XY: 0.0607 AC XY: 4520 AN XY: 74428

Gnomad4 AFR AF: 0.0616

Gnomad4 AMR AF: 0.0466

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0193

Gnomad4 NFE AF: 0.0573

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0637 Hom.: 293

Bravo AF: 0.0634

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 29, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Likely benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.086
Dann	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17082389; hg19: chr6-152577752; COSMIC: COSV54935033;