chr17-4498895-G-C

Position:

• chr17-4498895-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPNS2	NM_001124758.3	c.-153G>C		5_prime_UTR_variant	1/13	ENST00000329078.8	NP_001118230.1
SPNS2	XR_007065260.1	n.15G>C		non_coding_transcript_exon_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPNS2	ENST00000329078	c.-153G>C		5_prime_UTR_variant	1/13	1	NM_001124758.3	ENSP00000333292.3
SPNS2-AS1	ENST00000416958.1	n.48+732C>G		intron_variant		3

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

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.0480

Gnomad4 ASJ exome AF: 0.0759

Gnomad4 EAS exome AF: 0.00505

Gnomad4 SAS exome AF: 0.0417

Gnomad4 FIN exome AF: 0.0550

Gnomad4 NFE exome AF: 0.0620

Gnomad4 OTH exome AF: 0.0789

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

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.0624

Gnomad4 ASJ AF: 0.0803

Gnomad4 EAS AF: 0.0105

Gnomad4 SAS AF: 0.0545

Gnomad4 FIN AF: 0.0490

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0308 Hom.: 32

Asia WGS AF: 0.0340 AC: 104 AN: 3106

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.71

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: rs147646464; hg19: chr17-4402190;