Variant rs9371243 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.22191+42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,608,724 control chromosomes in the GnomAD database, including 47,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4014 hom., cov: 30)

Exomes 𝑓: 0.23 ( 43843 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.674

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:

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=-0.87).

BP6

Variant 6-152218215-C-G is Benign according to our data. Variant chr6-152218215-C-G is described in ClinVar as [Benign]. Clinvar id is 262183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 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.22191+42G>C		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.22191+42G>C		intron_variant		1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

31958

AN:

151654

Hom.:

4012

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.548

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.186

GnomAD3 exomes

AF:

0.265

AC:

66404

AN:

250676

Hom.:

10355

AF XY:

0.267

AC XY:

36134

AN XY:

135474

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.271

Gnomad EAS exome

AF:

0.571

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.345

Gnomad NFE exome

AF:

0.211

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.235

AC:

342126

AN:

1456952

Hom.:

43843

Cov.:

AF XY:

0.236

AC XY:

171261

AN XY:

725080

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.247

Gnomad4 ASJ exome

AF:

0.264

Gnomad4 EAS exome

AF:

0.526

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.341

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.240

GnomAD4 genome

AF:

0.211

AC:

31976

AN:

151772

Hom.:

4014

Cov.:

AF XY:

0.221

AC XY:

16345

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.548

Gnomad4 SAS

AF:

0.347

Gnomad4 FIN

AF:

0.354

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.213

Hom.:

677

Bravo

AF:

0.197

Asia WGS

AF:

0.406

AC:

1413

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 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.021

DANN

Benign

0.57

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