chr17-4513379-T-C

Position:

• chr17-4513379-T-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.436+67T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,545,488 control chromosomes in the GnomAD database, including 123,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14941 hom., cov: 34)
  • Exomes 𝑓: 0.39 (108887 hom.)
• Consequence: SPNS2 NM_001124758.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.45

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-4513379-T-C is Benign according to our data. Variant chr17-4513379-T-C is described in ClinVar as [Benign]. Clinvar id is 1271863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPNS2	NM_001124758.3	c.436+67T>C		intron_variant		ENST00000329078.8
SPNS2	XM_047435339.1	c.-18+67T>C		intron_variant
SPNS2	XR_007065260.1	n.603+67T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPNS2	ENST00000329078.8	c.436+67T>C		intron_variant		1	NM_001124758.3	P1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65433 AN: 152002 Hom.: 14922 Cov.: 34

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.391 AC: 544887 AN: 1393368 Hom.: 108887 AF XY: 0.394 AC XY: 272302 AN XY: 691320

Gnomad4 AFR exome AF: 0.586

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.180

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.366

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.431 AC: 65502 AN: 152120 Hom.: 14941 Cov.: 34 AF XY: 0.427 AC XY: 31799 AN XY: 74384

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.419

Alfa AF: 0.404 Hom.: 4020

Bravo AF: 0.434

Asia WGS AF: 0.352 AC: 1227 AN: 3478

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.35
DANN	Benign	0.35

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: rs7214270; hg19: chr17-4416674; COSMIC: COSV61230413;