7-100829641-G-A

Variant names:

• chr7-100829641-G-A
• rs2247445
• ENST00000856610.1:c.-43+2594G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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):

• neurodevelopmental disorder

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363494.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A9	NM_001363494.1		c.19+2594G>A		intron	N/A	NP_001350423.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A9	ENST00000856610.1		c.-43+2594G>A		intron	N/A	ENSP00000526669.1
	SLC12A9	ENST00000856609.1		c.-43+2594G>A		intron	N/A	ENSP00000526668.1
	SLC12A9	ENST00000971214.1		c.-142+2594G>A		intron	N/A	ENSP00000641273.1

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

African (AFR) AF: 0.101 AC: 4171 AN: 41412

American (AMR) AF: 0.387 AC: 5887 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3464

East Asian (EAS) AF: 0.571 AC: 2931 AN: 5132

South Asian (SAS) AF: 0.278 AC: 1336 AN: 4806

European-Finnish (FIN) AF: 0.183 AC: 1931 AN: 10530

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15922 AN: 67912

Other (OTH) AF: 0.251 AC: 527 AN: 2102

Alfa AF: 0.224 Hom.: 2031

Bravo AF: 0.232

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.7
DANN	Benign	0.49
PhyloP100		2.9

Splicing

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

Other links and lift over

dbSNP: rs2247445; hg19: chr7-100427263;