rs147646464

Variant names:

• chr17-4498895-G-C
• rs147646464
• NM_001124758.3:c.-153G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-4498895-G-C
• chr17-4498895-G-A
• chr17-4498895-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001124758.3(SPNS2):​c.-153G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 266,012 control chromosomes in the GnomAD database, including 2,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2481 hom., cov: 32)
  • Exomes 𝑓: 0.066 (372 hom.)
• Consequence: SPNS2 NM_001124758.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.45
• Publications: 0 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-4498895-G-C is Benign according to our data. Variant chr17-4498895-G-C is described in ClinVar as Benign. ClinVar VariationId is 1183043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

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.-153G>C		5_prime_UTR	Exon 1 of 13	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.-153G>C		5_prime_UTR	Exon 1 of 13	ENSP00000333292.3	Q8IVW8
	SPNS2	ENST00000947403.1		c.-153G>C		5_prime_UTR	Exon 1 of 13	ENSP00000617462.1
	SPNS2	ENST00000932033.1		c.-153G>C		5_prime_UTR	Exon 1 of 12	ENSP00000602092.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20584 AN: 150130 Hom.: 2477 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.0803

Gnomad EAS AF: 0.0103

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0490

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0662 AC: 7668 AN: 115774 Hom.: 372 Cov.: 4 AF XY: 0.0647 AC XY: 3607 AN XY: 55718

African (AFR) AF: 0.329 AC: 613 AN: 1862

American (AMR) AF: 0.0480 AC: 12 AN: 250

Ashkenazi Jewish (ASJ) AF: 0.0759 AC: 56 AN: 738

East Asian (EAS) AF: 0.00505 AC: 3 AN: 594

South Asian (SAS) AF: 0.0417 AC: 91 AN: 2184

European-Finnish (FIN) AF: 0.0550 AC: 22 AN: 400

Middle Eastern (MID) AF: 0.0682 AC: 15 AN: 220

European-Non Finnish (NFE) AF: 0.0620 AC: 6544 AN: 105570

Other (OTH) AF: 0.0789 AC: 312 AN: 3956

GnomAD4 genome AF: 0.137 AC: 20609 AN: 150238 Hom.: 2481 Cov.: 32 AF XY: 0.133 AC XY: 9777 AN XY: 73386

African (AFR) AF: 0.330 AC: 13606 AN: 41230

American (AMR) AF: 0.0624 AC: 944 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.0803 AC: 277 AN: 3448

East Asian (EAS) AF: 0.0105 AC: 54 AN: 5136

South Asian (SAS) AF: 0.0545 AC: 263 AN: 4822

European-Finnish (FIN) AF: 0.0490 AC: 484 AN: 9886

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0701 AC: 4720 AN: 67304

Other (OTH) AF: 0.104 AC: 216 AN: 2084

Alfa AF: 0.0308 Hom.: 32

Asia WGS AF: 0.0340 AC: 104 AN: 3106

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.71
PhyloP100		-1.5
PromoterAI		0.036	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs147646464; hg19: chr17-4402190;