17-4510732-A-G

Position:

• chr17-4510732-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001124758.3(SPNS2):​c.371-2515A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,064 control chromosomes in the GnomAD database, including 43,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.75 (43413 hom., cov: 31)
• Consequence: SPNS2 NM_001124758.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.553

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPNS2	NM_001124758.3	c.371-2515A>G		intron_variant		ENST00000329078.8
SPNS2	XM_047435339.1	c.-84+1040A>G		intron_variant
SPNS2	XR_007065260.1	n.538-2515A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPNS2	ENST00000329078.8	c.371-2515A>G		intron_variant		1	NM_001124758.3	P1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113846 AN: 151944 Hom.: 43375 Cov.: 31

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.735

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.749 AC: 113941 AN: 152064 Hom.: 43413 Cov.: 31 AF XY: 0.740 AC XY: 55027 AN XY: 74330

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.734

Alfa AF: 0.763 Hom.: 85689

Bravo AF: 0.741

Asia WGS AF: 0.526 AC: 1832 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Vascular endothelial growth factor (VEGF) inhibitor response Other:1

association, no assertion criteria provided

case-control

Department of Ophthalmology, College of Medicine, Hanyang University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs7213707; hg19: chr17-4414027;