Variant rs74709220 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.24977-1678T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,571,464 control chromosomes in the GnomAD database, including 1,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 106 hom., cov: 32)

Exomes 𝑓: 0.016 ( 1261 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.00

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=-0.81).

BP6

Variant 6-152145443-A-C is Benign according to our data. Variant chr6-152145443-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 262191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_001347702.2 linkuse as main transcript	c.1510+44T>G		intron_variant		ENST00000354674.5	NP_001334631.1
SYNE1	NM_182961.4 linkuse as main transcript	c.24977-1678T>G		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000354674.5 linkuse as main transcript	c.1510+44T>G		intron_variant		5	NM_001347702.2	ENSP00000346701
SYNE1	ENST00000367255.10 linkuse as main transcript	c.24977-1678T>G		intron_variant		1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1907

AN:

152128

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00500

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0300

AC:

7473

AN:

249170

Hom.:

462

AF XY:

0.0352

AC XY:

4745

AN XY:

134672

show subpopulations

Gnomad AFR exome

AF:

0.000871

Gnomad AMR exome

AF:

0.00204

Gnomad ASJ exome

AF:

0.0283

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.00551

Gnomad NFE exome

AF:

0.00485

Gnomad OTH exome

AF:

0.0218

GnomAD4 exome

AF:

0.0155

AC:

22016

AN:

1419218

Hom.:

1261

Cov.:

AF XY:

0.0193

AC XY:

13709

AN XY:

708654

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00222

Gnomad4 ASJ exome

AF:

0.0288

Gnomad4 EAS exome

AF:

0.127

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.00594

Gnomad4 NFE exome

AF:

0.00309

Gnomad4 OTH exome

AF:

0.0211

GnomAD4 genome

AF:

0.0125

AC:

1902

AN:

152246

Hom.:

106

Cov.:

AF XY:

0.0147

AC XY:

1094

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.0305

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.00631

Gnomad4 NFE

AF:

0.00500

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.00940

Hom.:

Bravo

AF:

0.00868

Asia WGS

AF:

0.126

AC:

437

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

not specified

Benign:1

Likely 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

-0.81

CADD

Benign

8.1

DANN

Benign

0.60

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