17-4530528-C-G

Variant summary

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

The NM_001124758.3(SPNS2):c.574-104C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,395,960 control chromosomes in the GnomAD database, including 2,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.057 (302 hom., cov: 32)
  • Exomes 𝑓: 0.053 (2013 hom.)
• Consequence: SPNS2 NM_001124758.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.619

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-4530528-C-G is Benign according to our data. Variant chr17-4530528-C-G is described in ClinVar as [Benign]. Clinvar id is 1234431.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPNS2	NM_001124758.3	c.574-104C>G		intron_variant		ENST00000329078.8
SPNS2	XM_047435339.1	c.121-104C>G		intron_variant
SPNS2	XR_007065260.1	n.741-104C>G		intron_variant, non_coding_transcript_variant
SPNS2	XR_007065261.1	n.411-104C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPNS2	ENST00000329078.8	c.574-104C>G		intron_variant		1	NM_001124758.3	P1

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 8699 AN: 151646 Hom.: 296 Cov.: 32

Gnomad AFR AF: 0.0555

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.0595

Gnomad MID AF: 0.0577

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.0679

GnomAD4 exome AF: 0.0532 AC: 66182 AN: 1244200 Hom.: 2013 AF XY: 0.0522 AC XY: 32223 AN XY: 616822

Gnomad4 AFR exome AF: 0.0550

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.0343

Gnomad4 EAS exome AF: 0.000131

Gnomad4 SAS exome AF: 0.0332

Gnomad4 FIN exome AF: 0.0626

Gnomad4 NFE exome AF: 0.0536

Gnomad4 OTH exome AF: 0.0495

GnomAD4 genome AF: 0.0574 AC: 8711 AN: 151760 Hom.: 302 Cov.: 32 AF XY: 0.0582 AC XY: 4315 AN XY: 74150

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.0595

Gnomad4 NFE AF: 0.0532

Gnomad4 OTH AF: 0.0671

Alfa AF: 0.0120 Hom.: 4

Bravo AF: 0.0618

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.88
Cadd	Benign	1.1
Dann	Benign	0.45

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: rs111597737; hg19: chr17-4433823;