rs3818110

Positions:

• chr6-152139926-G-A

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.25458+24C>T 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 1,610,822 control chromosomes in the GnomAD database, including 128,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14404 hom., cov: 31)
  • Exomes 𝑓: 0.39 (114285 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.287

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 6-152139926-G-A is Benign according to our data. Variant chr6-152139926-G-A is described in ClinVar as [Benign]. Clinvar id is 262193.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+24C>T		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4	c.25458+24C>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5	c.1992+24C>T		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10	c.25458+24C>T		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64863 AN: 151290 Hom.: 14403 Cov.: 31

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.468

GnomAD3 exomes AF: 0.408 AC: 101697 AN: 249532 Hom.: 21530 AF XY: 0.404 AC XY: 54569 AN XY: 134996

Gnomad AFR exome AF: 0.529

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.504

Gnomad EAS exome AF: 0.299

Gnomad SAS exome AF: 0.450

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.379

Gnomad OTH exome AF: 0.423

GnomAD4 exome AF: 0.392 AC: 571844 AN: 1459412 Hom.: 114285 Cov.: 35 AF XY: 0.393 AC XY: 285575 AN XY: 726014

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: 64914 AN: 151410 Hom.: 14404 Cov.: 31 AF XY: 0.425 AC XY: 31449 AN XY: 74000

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.467

Alfa AF: 0.408 Hom.: 3652

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

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- -

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3818110; hg19: chr6-152461061; COSMIC: COSV54896481;