rs790154

Positions:

• chr5-128165543-A-G
• chr5-128165543-A-T

Variant summary

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

The NM_001046.3(SLC12A2):​c.2617-2218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,162 control chromosomes in the GnomAD database, including 52,885 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 0.83 (52885 hom., cov: 31)
• Consequence: SLC12A2 NM_001046.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420

Genes affected

SLC12A2 (HGNC:10911): (solute carrier family 12 member 2) The protein encoded by this gene mediates sodium and chloride transport and reabsorption. The encoded protein is a membrane protein and is important in maintaining proper ionic balance and cell volume. This protein is phosphorylated in response to DNA damage. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

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 (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A2	NM_001046.3	c.2617-2218A>G		intron_variant		ENST00000262461.7	NP_001037.1
SLC12A2	NM_001256461.2	c.2617-2218A>G		intron_variant			NP_001243390.1
SLC12A2	XM_047417591.1	c.2617-2218A>G		intron_variant			XP_047273547.1
SLC12A2	NR_046207.2	n.2806-2218A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A2	ENST00000262461.7	c.2617-2218A>G		intron_variant		1	NM_001046.3	ENSP00000262461	P4

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125895 AN: 152044 Hom.: 52824 Cov.: 31

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.828 AC: 126010 AN: 152162 Hom.: 52885 Cov.: 31 AF XY: 0.831 AC XY: 61782 AN XY: 74390

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.793

Alfa AF: 0.787 Hom.: 21346

Bravo AF: 0.829

Asia WGS AF: 0.684 AC: 2374 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.64

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: rs790154; hg19: chr5-127501235;