Variant 6-152145447-A-G 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.24977-1682T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,581,206 control chromosomes in the GnomAD database, including 93,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10949 hom., cov: 31)

Exomes 𝑓: 0.33 ( 82081 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.983

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=-0.85).

BP6

Variant 6-152145447-A-G is Benign according to our data. Variant chr6-152145447-A-G is described in ClinVar as [Benign]. Clinvar id is 262190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_001347702.2 linkuse as main transcript	c.1510+40T>C		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4 linkuse as main transcript	c.24977-1682T>C		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5 linkuse as main transcript	c.1510+40T>C		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10 linkuse as main transcript	c.24977-1682T>C		intron_variant		1	NM_182961.4	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

56427

AN:

151762

Hom.:

10936

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.413

GnomAD3 exomes

AF:

0.364

AC:

90823

AN:

249238

Hom.:

17524

AF XY:

0.360

AC XY:

48544

AN XY:

134720

show subpopulations

Gnomad AFR exome

AF:

0.454

Gnomad AMR exome

AF:

0.511

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.302

Gnomad SAS exome

AF:

0.421

Gnomad FIN exome

AF:

0.223

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.334

AC:

477986

AN:

1429328

Hom.:

82081

Cov.:

AF XY:

0.336

AC XY:

239834

AN XY:

713170

show subpopulations

Gnomad4 AFR exome

AF:

0.442

Gnomad4 AMR exome

AF:

0.507

Gnomad4 ASJ exome

AF:

0.408

Gnomad4 EAS exome

AF:

0.310

Gnomad4 SAS exome

AF:

0.415

Gnomad4 FIN exome

AF:

0.225

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.350

GnomAD4 genome

AF:

0.372

AC:

56486

AN:

151878

Hom.:

10949

Cov.:

AF XY:

0.372

AC XY:

27617

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.447

Gnomad4 AMR

AF:

0.470

Gnomad4 ASJ

AF:

0.408

Gnomad4 EAS

AF:

0.312

Gnomad4 SAS

AF:

0.408

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.415

Alfa

AF:

0.340

Hom.:

15575

Bravo

AF:

0.395

Asia WGS

AF:

0.375

AC:

1302

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

-0.85

CADD

Benign

5.5

DANN

Benign

0.64

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