rs564065

Positions:

• chr3-125094678-C-G
• chr3-125094678-C-T

Variant summary

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

The NM_024628.6(SLC12A8):​c.1706-2480G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,024 control chromosomes in the GnomAD database, including 17,436 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 0.47 (17436 hom., cov: 32)
• Consequence: SLC12A8 NM_024628.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A8	NM_024628.6	c.1706-2480G>C		intron_variant		ENST00000469902.6	NP_078904.4
SLC12A8	NM_001195483.2	c.1706-2480G>C		intron_variant			NP_001182412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A8	ENST00000469902.6	c.1706-2480G>C		intron_variant		2	NM_024628.6	ENSP00000418783	P1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70967 AN: 151906 Hom.: 17432 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.467 AC: 71007 AN: 152024 Hom.: 17436 Cov.: 32 AF XY: 0.470 AC XY: 34969 AN XY: 74336

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.491

Alfa AF: 0.480 Hom.: 2233

Bravo AF: 0.459

Asia WGS AF: 0.640 AC: 2228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.70
DANN	Benign	0.56

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: rs564065; hg19: chr3-124813522;