rs651630

Variant names:

• chr3-125092470-G-A
• rs651630
• NM_024628.6:c.1706-272C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024628.6(SLC12A8):​c.1706-272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,012 control chromosomes in the GnomAD database, including 13,805 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 0.41 (13805 hom., cov: 31)
• Consequence: SLC12A8 NM_024628.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 12 publications found

Genes affected

SLC12A8 (HGNC:15595): (solute carrier family 12 member 8) This gene is thought to be a candidate for psoriasis susceptibility. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A8	NM_024628.6	c.1706-272C>T		intron_variant	Intron 10 of 13	ENST00000469902.6	NP_078904.4
SLC12A8	NM_001195483.2	c.1706-272C>T		intron_variant	Intron 9 of 12		NP_001182412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A8	ENST00000469902.6	c.1706-272C>T		intron_variant	Intron 10 of 13	2	NM_024628.6	ENSP00000418783.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61853 AN: 151894 Hom.: 13810 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.407 AC: 61870 AN: 152012 Hom.: 13805 Cov.: 31 AF XY: 0.408 AC XY: 30285 AN XY: 74280

African (AFR) AF: 0.214 AC: 8881 AN: 41476

American (AMR) AF: 0.360 AC: 5489 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1848 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2255 AN: 5172

South Asian (SAS) AF: 0.577 AC: 2777 AN: 4814

European-Finnish (FIN) AF: 0.467 AC: 4916 AN: 10536

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34170 AN: 67964

Other (OTH) AF: 0.419 AC: 885 AN: 2110

Alfa AF: 0.467 Hom.: 37899

Bravo AF: 0.388

Asia WGS AF: 0.512 AC: 1782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.85
DANN	Benign	0.24
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs651630; hg19: chr3-124811314; COSMIC: COSV58864471;