3-125136286-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024628.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A8	NM_024628.6	MANE Select	c.623-504G>A		intron	N/A	NP_078904.4
	SLC12A8	NM_001195483.2		c.623-504G>A		intron	N/A	NP_001182412.2	A0AV02-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A8	ENST00000469902.6	TSL:2 MANE Select	c.623-504G>A		intron	N/A	ENSP00000418783.1	A0AV02-1
	SLC12A8	ENST00000393469.8	TSL:1	c.623-504G>A		intron	N/A	ENSP00000377112.4	A0AV02-1
	SLC12A8	ENST00000895737.1		c.623-504G>A		intron	N/A	ENSP00000565796.1

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

African (AFR) AF: 0.0369 AC: 1533 AN: 41538

American (AMR) AF: 0.0962 AC: 1472 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3470

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5188

South Asian (SAS) AF: 0.130 AC: 626 AN: 4818

European-Finnish (FIN) AF: 0.198 AC: 2087 AN: 10552

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15403 AN: 67956

Other (OTH) AF: 0.140 AC: 296 AN: 2108

Alfa AF: 0.151 Hom.: 1482

Bravo AF: 0.131

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.78
PhyloP100		-0.47
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs28986275; hg19: chr3-124855130;