Variant rs214968 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.2728-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,611,340 control chromosomes in the GnomAD database, including 48,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5955 hom., cov: 33)

Exomes 𝑓: 0.24 ( 42397 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0830

Variant links:

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]

SYNE1 links:

SYNE1 (HGNC:):

SYNE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-152455615-G-A is Benign according to our data. Variant chr6-152455615-G-A is described in ClinVar as [Benign]. Clinvar id is 262195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152455615-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.2728-25C>T		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.2728-25C>T		intron_variant		1	NM_182961.4	ENSP00000356224.5		Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41189

AN:

151982

Hom.:

5948

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.274

GnomAD3 exomes

AF:

0.251

AC:

63081

AN:

251076

Hom.:

8333

AF XY:

0.252

AC XY:

34141

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.371

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.335

Gnomad SAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.238

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.236

AC:

344897

AN:

1459242

Hom.:

42397

Cov.:

AF XY:

0.238

AC XY:

172975

AN XY:

726124

show subpopulations

Gnomad4 AFR exome

AF:

0.366

Gnomad4 AMR exome

AF:

0.218

Gnomad4 ASJ exome

AF:

0.229

Gnomad4 EAS exome

AF:

0.351

Gnomad4 SAS exome

AF:

0.286

Gnomad4 FIN exome

AF:

0.185

Gnomad4 NFE exome

AF:

0.227

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.271

AC:

41232

AN:

152098

Hom.:

5955

Cov.:

AF XY:

0.268

AC XY:

19887

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.364

Gnomad4 AMR

AF:

0.240

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.327

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.181

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.275

Alfa

AF:

0.261

Hom.:

1106

Bravo

AF:

0.281

Asia WGS

AF:

0.292

AC:

1018

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 14, 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

-0.81

CADD

Benign

0.31

DANN

Benign

0.26

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over