Variant chr6-152484754-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_182961.4(SYNE1):c.1185+81G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,474,156 control chromosomes in the GnomAD database, including 154,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.52 ( 22302 hom., cov: 33)

Exomes 𝑓: 0.44 ( 132476 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.470

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 6-152484754-C-T is Benign according to our data. Variant chr6-152484754-C-T is described in ClinVar as [Benign]. Clinvar id is 670600.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.1185+81G>A		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 link	c.1185+81G>A		intron_variant		1	NM_182961.4	ENSP00000356224.5		Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

79070

AN:

151934

Hom.:

22261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.725

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.758

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.525

GnomAD4 exome

AF:

0.438

AC:

579449

AN:

1322104

Hom.:

132476

AF XY:

0.441

AC XY:

292391

AN XY:

662424

show subpopulations

Gnomad4 AFR exome

AF:

0.732

Gnomad4 AMR exome

AF:

0.338

Gnomad4 ASJ exome

AF:

0.482

Gnomad4 EAS exome

AF:

0.780

Gnomad4 SAS exome

AF:

0.524

Gnomad4 FIN exome

AF:

0.404

Gnomad4 NFE exome

AF:

0.412

Gnomad4 OTH exome

AF:

0.470

GnomAD4 genome

AF:

0.521

AC:

79161

AN:

152052

Hom.:

22302

Cov.:

AF XY:

0.519

AC XY:

38610

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.725

Gnomad4 AMR

AF:

0.424

Gnomad4 ASJ

AF:

0.490

Gnomad4 EAS

AF:

0.758

Gnomad4 SAS

AF:

0.542

Gnomad4 FIN

AF:

0.399

Gnomad4 NFE

AF:

0.422

Gnomad4 OTH

AF:

0.524

Alfa

AF:

0.468

Hom.:

3001

Bravo

AF:

0.530

Asia WGS

AF:

0.631

AC:

2196

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.88

CADD

Benign

0.28

DANN

Benign

0.40

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