3-125173702-A-G

Position:

• chr3-125173702-A-G

Variant summary

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

The NM_024628.6(SLC12A8):​c.622+4041T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,270 control chromosomes in the GnomAD database, including 61,797 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 0.90 (61797 hom., cov: 32)
• Consequence: SLC12A8 NM_024628.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A8	NM_024628.6	c.622+4041T>C		intron_variant		ENST00000469902.6	NP_078904.4
SLC12A8	NM_001195483.2	c.622+4041T>C		intron_variant			NP_001182412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A8	ENST00000469902.6	c.622+4041T>C		intron_variant		2	NM_024628.6	ENSP00000418783.1
SLC12A8	ENST00000393469.8	c.622+4041T>C		intron_variant		1		ENSP00000377112.4
SLC12A8	ENST00000479826.1	c.268+13535T>C		intron_variant		3		ENSP00000420197.1
SLC12A8	ENST00000473262.5	n.*84+4041T>C		intron_variant		5		ENSP00000419424.1

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136528 AN: 152152 Hom.: 61756 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.944

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.910

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

GnomAD4 genome AF: 0.897 AC: 136625 AN: 152270 Hom.: 61797 Cov.: 32 AF XY: 0.896 AC XY: 66758 AN XY: 74470

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.949

Gnomad4 ASJ AF: 0.944

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.978

Gnomad4 NFE AF: 0.949

Gnomad4 OTH AF: 0.909

Alfa AF: 0.941 Hom.: 103007

Bravo AF: 0.894

Asia WGS AF: 0.784 AC: 2727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	11
DANN	Benign	0.83

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: rs503875; hg19: chr3-124892546;