rs6557210

chr6-152249280-G-Achr6-152249280-G-Cchr6-152249280-G-T

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.19471-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 1,470,016 control chromosomes in the GnomAD database, including 301,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32283 hom., cov: 32)
  • Exomes 𝑓: 0.64 (269096 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.90

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 6-152249280-G-A is Benign according to our data. Variant chr6-152249280-G-A is described in ClinVar as [Benign]. Clinvar id is 262176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152249280-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.19471-18C>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.19471-18C>T		intron_variant		1	NM_182961.4	P1
SYNE1	ENST00000423061.6	c.19258-18C>T		intron_variant		1
SYNE1	ENST00000367256.9	n.3163-18C>T		intron_variant, non_coding_transcript_variant		1
SYNE1	ENST00000409694.6	n.3055-18C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98262 AN: 151940 Hom.: 32247 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.596

GnomAD3 exomes AF: 0.658 AC: 165266 AN: 250984 Hom.: 55523 AF XY: 0.655 AC XY: 88848 AN XY: 135654

Gnomad AFR exome AF: 0.655

Gnomad AMR exome AF: 0.621

Gnomad ASJ exome AF: 0.610

Gnomad EAS exome AF: 0.895

Gnomad SAS exome AF: 0.662

Gnomad FIN exome AF: 0.780

Gnomad NFE exome AF: 0.613

Gnomad OTH exome AF: 0.642

GnomAD4 exome AF: 0.637 AC: 839004 AN: 1317958 Hom.: 269096 Cov.: 20 AF XY: 0.635 AC XY: 421899 AN XY: 664054

Gnomad4 AFR exome AF: 0.654

Gnomad4 AMR exome AF: 0.623

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.878

Gnomad4 SAS exome AF: 0.661

Gnomad4 FIN exome AF: 0.782

Gnomad4 NFE exome AF: 0.618

Gnomad4 OTH exome AF: 0.643

GnomAD4 genome AF: 0.647 AC: 98349 AN: 152058 Hom.: 32283 Cov.: 32 AF XY: 0.654 AC XY: 48651 AN XY: 74350

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.882

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.786

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.601

Alfa AF: 0.607 Hom.: 31771

Bravo AF: 0.635

Asia WGS AF: 0.769 AC: 2673 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 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, no assertion criteria provided	clinical testing	Clinical Genetics, Academic 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

- -

Arthrogryposis multiplex congenita 3, myogenic type Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Autosomal recessive ataxia, Beauce type Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.0
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: rs6557210; hg19: chr6-152570415; COSMIC: COSV54939047;