Variant rs147380321 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.25458+33_25458+36del 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 1,609,670 control chromosomes in the GnomAD database, including 128,539 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14403 hom., cov: 0)

Exomes 𝑓: 0.39 ( 114136 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.01

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 -16 ACMG points.

BP6

Variant 6-152139913-CTGTT-C is Benign according to our data. Variant chr6-152139913-CTGTT-C is described in ClinVar as [Benign]. Clinvar id is 262194.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 linkuse as main transcript	c.1992+33_1992+36del		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4 linkuse as main transcript	c.25458+33_25458+36del		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5 linkuse as main transcript	c.1992+33_1992+36del		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10 linkuse as main transcript	c.25458+33_25458+36del		intron_variant		1	NM_182961.4	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

64832

AN:

151286

Hom.:

14402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.497

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.468

GnomAD3 exomes

AF:

0.407

AC:

101053

AN:

248474

Hom.:

21204

AF XY:

0.403

AC XY:

54194

AN XY:

134422

show subpopulations

Gnomad AFR exome

AF:

0.528

Gnomad AMR exome

AF:

0.531

Gnomad ASJ exome

AF:

0.503

Gnomad EAS exome

AF:

0.299

Gnomad SAS exome

AF:

0.450

Gnomad FIN exome

AF:

0.249

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.423

GnomAD4 exome

AF:

0.392

AC:

571247

AN:

1458264

Hom.:

114136

AF XY:

0.393

AC XY:

285313

AN XY:

725494

show subpopulations

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:

64883

AN:

151406

Hom.:

14403

Cov.:

AF XY:

0.425

AC XY:

31434

AN XY:

73994

show subpopulations

Gnomad4 AFR

AF:

0.525

Gnomad4 AMR

AF:

0.498

Gnomad4 ASJ

AF:

0.501

Gnomad4 EAS

AF:

0.308

Gnomad4 SAS

AF:

0.436

Gnomad4 FIN

AF:

0.245

Gnomad4 NFE

AF:

0.387

Gnomad4 OTH

AF:

0.467

Alfa

AF:

0.415

Hom.:

2389

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

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 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

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