7-100855586-T-C

Position:

• chr7-100855586-T-C

Variant summary

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

The NM_020246.4(SLC12A9):​c.317-120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,349,510 control chromosomes in the GnomAD database, including 21,384 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 0.14 (1795 hom., cov: 32)
  • Exomes 𝑓: 0.17 (19589 hom.)
• Consequence: SLC12A9 NM_020246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A9	NM_020246.4	c.317-120T>C		intron_variant		ENST00000354161.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A9	ENST00000354161.8	c.317-120T>C		intron_variant		1	NM_020246.4	P1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20876 AN: 152142 Hom.: 1800 Cov.: 32

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0351

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.174 AC: 208702 AN: 1197250 Hom.: 19589 Cov.: 15 AF XY: 0.173 AC XY: 104136 AN XY: 601366

Gnomad4 AFR exome AF: 0.0488

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.0273

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.137 AC: 20868 AN: 152260 Hom.: 1795 Cov.: 32 AF XY: 0.136 AC XY: 10110 AN XY: 74458

Gnomad4 AFR AF: 0.0514

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0346

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.143

Alfa AF: 0.173 Hom.: 3715

Bravo AF: 0.126

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.8
DANN	Benign	0.63

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: rs314370; hg19: chr7-100453208; COSMIC: COSV51933973; COSMIC: COSV51933973;