rs7801190

Variant names:

• chr7-100860471-C-G
• rs7801190
• NM_020246.4:c.1218+239C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020246.4(SLC12A9):​c.1218+239C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 551,228 control chromosomes in the GnomAD database, including 2,107 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 0.096 (1247 hom., cov: 33)
  • Exomes 𝑓: 0.053 (860 hom.)
• Consequence: SLC12A9 NM_020246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700
• Publications: 24 publications found

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]

SLC12A9 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A9	NM_020246.4	c.1218+239C>G		intron_variant	Intron 9 of 13	ENST00000354161.8	NP_064631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A9	ENST00000354161.8	c.1218+239C>G		intron_variant	Intron 9 of 13	1	NM_020246.4	ENSP00000275730.4

Frequencies

GnomAD3 genomes AF: 0.0958 AC: 14530 AN: 151656 Hom.: 1241 Cov.: 33

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.0989

Gnomad EAS AF: 0.000585

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.0295

Gnomad MID AF: 0.0994

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0985

GnomAD4 exome AF: 0.0525 AC: 20977 AN: 399454 Hom.: 860 Cov.: 3 AF XY: 0.0536 AC XY: 11249 AN XY: 210060

African (AFR) AF: 0.216 AC: 2471 AN: 11442

American (AMR) AF: 0.0516 AC: 697 AN: 13510

Ashkenazi Jewish (ASJ) AF: 0.0987 AC: 1230 AN: 12464

East Asian (EAS) AF: 0.000260 AC: 7 AN: 26962

South Asian (SAS) AF: 0.0627 AC: 2538 AN: 40456

European-Finnish (FIN) AF: 0.0301 AC: 779 AN: 25852

Middle Eastern (MID) AF: 0.103 AC: 203 AN: 1964

European-Non Finnish (NFE) AF: 0.0476 AC: 11605 AN: 243638

Other (OTH) AF: 0.0625 AC: 1447 AN: 23166

GnomAD4 genome AF: 0.0960 AC: 14563 AN: 151774 Hom.: 1247 Cov.: 33 AF XY: 0.0935 AC XY: 6930 AN XY: 74152

African (AFR) AF: 0.225 AC: 9294 AN: 41340

American (AMR) AF: 0.0615 AC: 938 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0989 AC: 343 AN: 3468

East Asian (EAS) AF: 0.000586 AC: 3 AN: 5116

South Asian (SAS) AF: 0.0611 AC: 293 AN: 4798

European-Finnish (FIN) AF: 0.0295 AC: 312 AN: 10562

Middle Eastern (MID) AF: 0.100 AC: 29 AN: 290

European-Non Finnish (NFE) AF: 0.0462 AC: 3139 AN: 67930

Other (OTH) AF: 0.0970 AC: 205 AN: 2114

Alfa AF: 0.0555 Hom.: 182

Bravo AF: 0.103

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.54
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7801190; hg19: chr7-100458093;