chr3-125136286-C-T

Variant names:

• chr3-125136286-C-T
• rs28986275
• NM_024628.6:c.623-504G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024628.6(SLC12A8):​c.623-504G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,130 control chromosomes in the GnomAD database, including 2,234 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 0.15 (2234 hom., cov: 31)
• Consequence: SLC12A8 NM_024628.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A8	NM_024628.6	c.623-504G>A		intron_variant	Intron 5 of 13	ENST00000469902.6	NP_078904.4
SLC12A8	NM_001195483.2	c.623-504G>A		intron_variant	Intron 4 of 12		NP_001182412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A8	ENST00000469902.6	c.623-504G>A		intron_variant	Intron 5 of 13	2	NM_024628.6	ENSP00000418783.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22195 AN: 152012 Hom.: 2234 Cov.: 31

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0964

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.146 AC: 22190 AN: 152130 Hom.: 2234 Cov.: 31 AF XY: 0.143 AC XY: 10597 AN XY: 74348

Gnomad4 AFR AF: 0.0369

Gnomad4 AMR AF: 0.0962

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.140

Alfa AF: 0.157 Hom.: 794

Bravo AF: 0.131

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.78

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: rs28986275; hg19: chr3-124855130;