rs76790474

Variant names:

• chr17-4498679-G-A
• rs76790474
• ENST00000809725.1:n.91C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000809725.1(SPNS2-AS1):​n.91C>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 ENST00000809725.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.979
• Publications: 1 publications found

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]

SPNS2 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive 115

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000809725.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPNS2	NM_001124758.3	MANE Select	c.-369G>A		upstream_gene	N/A	NP_001118230.1	Q8IVW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPNS2-AS1	ENST00000809725.1		n.91C>T		non_coding_transcript_exon	Exon 1 of 2
	SPNS2-AS1	ENST00000416958.2	TSL:3	n.287+948C>T		intron	N/A
	SPNS2-AS1	ENST00000809720.1		n.253+948C>T		intron	N/A

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

African (AFR) AF: 0.0430 AC: 1784 AN: 41532

American (AMR) AF: 0.148 AC: 2260 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3470

East Asian (EAS) AF: 0.181 AC: 933 AN: 5146

South Asian (SAS) AF: 0.295 AC: 1424 AN: 4824

European-Finnish (FIN) AF: 0.252 AC: 2657 AN: 10564

Middle Eastern (MID) AF: 0.176 AC: 51 AN: 290

European-Non Finnish (NFE) AF: 0.232 AC: 15713 AN: 67864

Other (OTH) AF: 0.163 AC: 345 AN: 2112

Alfa AF: 0.201 Hom.: 525

Bravo AF: 0.153

Asia WGS AF: 0.207 AC: 717 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.90
PhyloP100		-0.98
PromoterAI		-0.021	Neutral

Splicing

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

Other links and lift over

dbSNP: rs76790474; hg19: chr17-4401974;