17-4499508-T-G

Variant names:

• chr17-4499508-T-G
• rs184566
• NM_001124758.3:c.370+91T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001124758.3(SPNS2):​c.370+91T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000723 in 152,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000046 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPNS2 NM_001124758.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.954
• Publications: 4 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001124758.3. 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.370+91T>G		intron	N/A	NP_001118230.1	Q8IVW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPNS2	ENST00000329078.8	TSL:1 MANE Select	c.370+91T>G		intron	N/A	ENSP00000333292.3	Q8IVW8
	SPNS2	ENST00000947403.1		c.370+91T>G		intron	N/A	ENSP00000617462.1
	SPNS2	ENST00000932033.1		c.370+91T>G		intron	N/A	ENSP00000602092.1

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 151976 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000460 AC: 33 AN: 717258 Hom.: 0 Cov.: 9 AF XY: 0.0000450 AC XY: 16 AN XY: 355522

African (AFR) AF: 0.00 AC: 0 AN: 14648

American (AMR) AF: 0.00 AC: 0 AN: 8544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12930

East Asian (EAS) AF: 0.000445 AC: 11 AN: 24722

South Asian (SAS) AF: 0.00 AC: 0 AN: 33408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2392

European-Non Finnish (NFE) AF: 0.00000178 AC: 1 AN: 561774

Other (OTH) AF: 0.000651 AC: 21 AN: 32274

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152094 Hom.: 0 Cov.: 30 AF XY: 0.0000673 AC XY: 5 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41504

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00197 AC: 10 AN: 5082

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67968

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00 Hom.: 3328

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.8
DANN	Benign	0.56
PhyloP100		0.95

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

Other links and lift over

dbSNP: rs184566; hg19: chr17-4402803;