rs76790474

Variant names:

• chr17-4498679-G-A
• rs76790474
• XR_001752762.1:n.38C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The XR_001752762.1(SPNS2-AS1):​n.38C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,996 control chromosomes in the GnomAD database, including 2,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2828 hom., cov: 32)
• Consequence: SPNS2-AS1 XR_001752762.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.979

Genes affected

SPNS2-AS1 (HGNC:55787): (SPNS2 antisense RNA 1)

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-4498679-G-A is Benign according to our data. Variant chr17-4498679-G-A is described in ClinVar as [Benign]. Clinvar id is 1273221.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPNS2	NM_001124758.3	c.-369G>A		upstream_gene_variant		ENST00000329078.8	NP_001118230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPNS2-AS1	ENST00000416958.1	n.48+948C>T		intron_variant	Intron 1 of 1	3
SPNS2	ENST00000329078.8	c.-369G>A		upstream_gene_variant		1	NM_001124758.3	ENSP00000333292.3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25728 AN: 151878 Hom.: 2818 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.173

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.169 AC: 25740 AN: 151996 Hom.: 2828 Cov.: 32 AF XY: 0.172 AC XY: 12746 AN XY: 74318

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.163

Alfa AF: 0.201 Hom.: 525

Bravo AF: 0.153

Asia WGS AF: 0.207 AC: 717 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs76790474; hg19: chr17-4401974;