Variant 17-4513343-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001124758.3(SPNS2):c.436+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,610,152 control chromosomes in the GnomAD database, including 92,553 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9497 hom., cov: 33)

Exomes 𝑓: 0.33 ( 83056 hom. )

Consequence

SPNS2
NM_001124758.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.95

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-4513343-G-A is Benign according to our data. Variant chr17-4513343-G-A is described in ClinVar as [Benign]. Clinvar id is 1240719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
SPNS2	NM_001124758.3 linkuse as main transcript	c.436+31G>A	intron_variant	ENST00000329078.8
SPNS2	XM_047435339.1 linkuse as main transcript	c.-18+31G>A	intron_variant
SPNS2	XR_007065260.1 linkuse as main transcript	n.603+31G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPNS2	ENST00000329078.8 linkuse as main transcript	c.436+31G>A		intron_variant		1	NM_001124758.3	P1

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52900

AN:

151946

Hom.:

9476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.340

GnomAD3 exomes

AF:

0.331

AC:

81611

AN:

246700

Hom.:

13956

AF XY:

0.335

AC XY:

44985

AN XY:

134338

show subpopulations

Gnomad AFR exome

AF:

0.424

Gnomad AMR exome

AF:

0.317

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.213

Gnomad SAS exome

AF:

0.411

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.327

Gnomad OTH exome

AF:

0.330

GnomAD4 exome

AF:

0.334

AC:

487225

AN:

1458088

Hom.:

83056

Cov.:

AF XY:

0.336

AC XY:

243857

AN XY:

725000

show subpopulations

Gnomad4 AFR exome

AF:

0.415

Gnomad4 AMR exome

AF:

0.317

Gnomad4 ASJ exome

AF:

0.260

Gnomad4 EAS exome

AF:

0.179

Gnomad4 SAS exome

AF:

0.411

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.337

GnomAD4 genome

AF:

0.348

AC:

52973

AN:

152064

Hom.:

9497

Cov.:

AF XY:

0.348

AC XY:

25846

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.414

Gnomad4 AMR

AF:

0.322

Gnomad4 ASJ

AF:

0.258

Gnomad4 EAS

AF:

0.213

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.328

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.342

Alfa

AF:

0.325

Hom.:

1499

Bravo

AF:

0.348

Asia WGS

AF:

0.310

AC:

1082

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	- -

Hearing loss, autosomal recessive 115

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.099

DANN

Benign

0.87

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over