rs147380321

chr6-152139913-CTGTT-Cchr6-152139913-CTGTT-CTGTTTGTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_182961.4(SYNE1):c.25458+33_25458+36del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,609,670 control chromosomes in the GnomAD database, including 128,539 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14403 hom., cov: 0)
  • Exomes 𝑓: 0.39 (114136 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01

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 -16 ACMG points.

• BP6: Variant 6-152139913-CTGTT-C is Benign according to our data. Variant chr6-152139913-CTGTT-C is described in ClinVar as [Benign]. Clinvar id is 262194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_001347702.2	c.1992+33_1992+36del		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4	c.25458+33_25458+36del		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5	c.1992+33_1992+36del		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10	c.25458+33_25458+36del		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64832 AN: 151286 Hom.: 14402 Cov.: 0

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.468

GnomAD3 exomes AF: 0.407 AC: 101053 AN: 248474 Hom.: 21204 AF XY: 0.403 AC XY: 54194 AN XY: 134422

Gnomad AFR exome AF: 0.528

Gnomad AMR exome AF: 0.531

Gnomad ASJ exome AF: 0.503

Gnomad EAS exome AF: 0.299

Gnomad SAS exome AF: 0.450

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.378

Gnomad OTH exome AF: 0.423

GnomAD4 exome AF: 0.392 AC: 571247 AN: 1458264 Hom.: 114136 AF XY: 0.393 AC XY: 285313 AN XY: 725494

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.532

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.308

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.384

Gnomad4 OTH exome AF: 0.407

GnomAD4 genome AF: 0.429 AC: 64883 AN: 151406 Hom.: 14403 Cov.: 0 AF XY: 0.425 AC XY: 31434 AN XY: 73994

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.467

Alfa AF: 0.415 Hom.: 2389

Bravo AF: 0.458

Asia WGS AF: 0.363 AC: 1260 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 18, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs147380321; hg19: chr6-152461048;