Variant 17-4530667-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001124758.3(SPNS2):c.609G>A(p.Val203=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,613,632 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 41 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 36 hom. )

Consequence

SPNS2
NM_001124758.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.622

Variant links:

Genes affected

SPNS2 (HGNC:26992): (SPNS lysolipid transporter 2, sphingosine-1-phosphate) The protein encoded by this gene is a transporter of sphingosine 1-phosphate, a secreted lipid that is important in cardiovascular, immunological, and neural development. Defects in this gene are a cause of early onset progressive hearing loss. [provided by RefSeq, Jul 2016]

SPNS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 17-4530667-G-A is Benign according to our data. Variant chr17-4530667-G-A is described in ClinVar as [Benign]. Clinvar id is 3050164.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.622 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2039/152300) while in subpopulation AFR AF= 0.047 (1955/41554). AF 95% confidence interval is 0.0453. There are 41 homozygotes in gnomad4. There are 962 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPNS2	NM_001124758.3 linkuse as main transcript	c.609G>A	p.Val203=	synonymous_variant	4/13	ENST00000329078.8
SPNS2	XM_047435339.1 linkuse as main transcript	c.156G>A	p.Val52=	synonymous_variant	4/13
SPNS2	XR_007065260.1 linkuse as main transcript	n.776G>A		non_coding_transcript_exon_variant	4/13
SPNS2	XR_007065261.1 linkuse as main transcript	n.446G>A		non_coding_transcript_exon_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPNS2	ENST00000329078.8 linkuse as main transcript	c.609G>A	p.Val203=	synonymous_variant	4/13	1	NM_001124758.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2030

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0470

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00307

AC:

762

AN:

248594

Hom.:

AF XY:

0.00240

AC XY:

324

AN XY:

135072

show subpopulations

Gnomad AFR exome

AF:

0.0433

Gnomad AMR exome

AF:

0.00197

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00137

AC:

2008

AN:

1461332

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

872

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.0486

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000684

Gnomad4 OTH exome

AF:

0.00313

GnomAD4 genome

AF:

0.0134

AC:

2039

AN:

152300

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

962

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0470

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00687

Hom.:

Bravo

AF:

0.0149

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SPNS2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

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