Variant rs2348080 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_182961.4(SYNE1):c.24450+28A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0406 in 1,613,058 control chromosomes in the GnomAD database, including 1,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.043 ( 171 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1359 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:

SYNE1 (HGNC:):

SYNE1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 6-152151525-T-A is Benign according to our data. Variant chr6-152151525-T-A is described in ClinVar as [Benign]. Clinvar id is 262189.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0429 (6536/152242) while in subpopulation AMR AF= 0.0505 (772/15300). AF 95% confidence interval is 0.0475. There are 171 homozygotes in gnomad4. There are 3183 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 6536 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.24450+28A>T		intron_variant		ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2 linkuse as main transcript	c.915+28A>T		intron_variant		ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.24450+28A>T		intron_variant		1	NM_182961.4	ENSP00000356224.5		Q8NF91-1
SYNE1	ENST00000354674.5 linkuse as main transcript	c.915+28A>T		intron_variant		5	NM_001347702.2	ENSP00000346701.4		F8WAI0

Frequencies

GnomAD3 genomes

AF:

0.0428

AC:

6516

AN:

152124

Hom.:

170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0461

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.0507

Gnomad ASJ

AF:

0.0926

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0193

Gnomad FIN

AF:

0.0428

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0411

Gnomad OTH

AF:

0.0578

GnomAD3 exomes

AF:

0.0383

AC:

9565

AN:

249744

Hom.:

233

AF XY:

0.0378

AC XY:

5107

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.0468

Gnomad AMR exome

AF:

0.0332

Gnomad ASJ exome

AF:

0.0882

Gnomad EAS exome

AF:

0.000817

Gnomad SAS exome

AF:

0.0194

Gnomad FIN exome

AF:

0.0430

Gnomad NFE exome

AF:

0.0440

Gnomad OTH exome

AF:

0.0478

GnomAD4 exome

AF:

0.0403

AC:

58928

AN:

1460816

Hom.:

1359

Cov.:

AF XY:

0.0398

AC XY:

28919

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.0460

Gnomad4 AMR exome

AF:

0.0345

Gnomad4 ASJ exome

AF:

0.0933

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0189

Gnomad4 FIN exome

AF:

0.0438

Gnomad4 NFE exome

AF:

0.0417

Gnomad4 OTH exome

AF:

0.0459

GnomAD4 genome

AF:

0.0429

AC:

6536

AN:

152242

Hom.:

171

Cov.:

AF XY:

0.0428

AC XY:

3183

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0463

Gnomad4 AMR

AF:

0.0505

Gnomad4 ASJ

AF:

0.0926

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0191

Gnomad4 FIN

AF:

0.0428

Gnomad4 NFE

AF:

0.0411

Gnomad4 OTH

AF:

0.0610

Alfa

AF:

0.0498

Hom.:

Bravo

AF:

0.0433

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.2

DANN

Benign

0.34

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