chr14-63702147-G-A

Position:

• chr14-63702147-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_030791.4(SGPP1):​c.685-3489C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 152,160 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.016 (29 hom., cov: 31)
• Consequence: SGPP1 NM_030791.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231

Genes affected

SGPP1 (HGNC:17720): (sphingosine-1-phosphate phosphatase 1) Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that regulates diverse biologic processes. SGPP1 catalyzes the degradation of S1P via salvage and recycling of sphingosine into long-chain ceramides (Mandala et al., 2000 [PubMed 10859351]; Le Stunff et al., 2007 [PubMed 17895250]).[supplied by OMIM, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0155 (2364/152160) while in subpopulation NFE AF= 0.0242 (1643/68000). AF 95% confidence interval is 0.0232. There are 29 homozygotes in gnomad4. There are 1163 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2364 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGPP1	NM_030791.4	c.685-3489C>T		intron_variant		ENST00000247225.7	NP_110418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGPP1	ENST00000247225.7	c.685-3489C>T		intron_variant		1	NM_030791.4	ENSP00000247225	P1

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2363 AN: 152042 Hom.: 29 Cov.: 31

Gnomad AFR AF: 0.00415

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.00767

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00748

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0242

Gnomad OTH AF: 0.0158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0155 AC: 2364 AN: 152160 Hom.: 29 Cov.: 31 AF XY: 0.0156 AC XY: 1163 AN XY: 74380

Gnomad4 AFR AF: 0.00414

Gnomad4 AMR AF: 0.00766

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00748

Gnomad4 FIN AF: 0.0308

Gnomad4 NFE AF: 0.0242

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0216 Hom.: 14

Bravo AF: 0.0138

Asia WGS AF: 0.00404 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11624105; hg19: chr14-64168865;