rs2247445

chr7-100829641-G-Achr7-100829641-G-T

Variant summary

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

The NM_001363494.1(SLC12A9):c.19+2594G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,780 control chromosomes in the GnomAD database, including 4,713 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 0.22 (4713 hom., cov: 31)
• Consequence: SLC12A9 NM_001363494.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

Genes affected

SLC12A9 (HGNC:17435): (solute carrier family 12 member 9) Predicted to enable potassium:chloride symporter activity. Predicted to be involved in cell volume homeostasis; inorganic ion homeostasis; and inorganic ion transmembrane transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A9	NM_001363494.1	c.19+2594G>A		intron_variant
SLC12A9	XM_047420627.1	c.-859+2594G>A		intron_variant
SLC12A9	XM_047420628.1	c.-43+2594G>A		intron_variant
SLC12A9	XM_047420632.1	c.-121+1392G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A9	ENST00000461016.1	n.228+2594G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33615 AN: 151662 Hom.: 4708 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.222 AC: 33628 AN: 151780 Hom.: 4713 Cov.: 31 AF XY: 0.228 AC XY: 16878 AN XY: 74160

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.251

Alfa AF: 0.226 Hom.: 1802

Bravo AF: 0.232

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.7
Dann	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2247445; hg19: chr7-100427263;