11-128871185-T-C

Variant names:

• chr11-128871185-T-C
• rs4529890
• ENST00000923294.1:c.-296+82A>G

Variant summary

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

The ENST00000923294.1(KCNJ1):​c.-296+82A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,238 control chromosomes in the GnomAD database, including 59,497 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 0.88 (59497 hom., cov: 32)
• Consequence: KCNJ1 ENST00000923294.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 2 publications found

Genes affected

KCNJ1 (HGNC:6255): (potassium inwardly rectifying channel subfamily J member 1) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. It is activated by internal ATP and probably plays an important role in potassium homeostasis. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Mutations in this gene have been associated with antenatal Bartter syndrome, which is characterized by salt wasting, hypokalemic alkalosis, hypercalciuria, and low blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KCNJ1 Gene-Disease associations (from GenCC):

• Bartter disease type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• antenatal Bartter syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 = 0.93 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000923294.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ1	ENST00000923294.1		c.-296+82A>G		intron	N/A	ENSP00000593353.1
	KCNJ1	ENST00000923295.1		c.-398A>G		upstream_gene	N/A	ENSP00000593354.1
	KCNJ1	ENST00000923296.1		c.-568A>G		upstream_gene	N/A	ENSP00000593355.1

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134360 AN: 152120 Hom.: 59451 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.883 AC: 134461 AN: 152238 Hom.: 59497 Cov.: 32 AF XY: 0.881 AC XY: 65599 AN XY: 74438

African (AFR) AF: 0.938 AC: 38971 AN: 41554

American (AMR) AF: 0.912 AC: 13959 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3114 AN: 3466

East Asian (EAS) AF: 0.890 AC: 4603 AN: 5174

South Asian (SAS) AF: 0.749 AC: 3612 AN: 4822

European-Finnish (FIN) AF: 0.844 AC: 8948 AN: 10600

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58309 AN: 68002

Other (OTH) AF: 0.880 AC: 1863 AN: 2116

Alfa AF: 0.877 Hom.: 15784

Bravo AF: 0.892

Asia WGS AF: 0.829 AC: 2886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.87
PhyloP100		-0.14

Splicing

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

Other links and lift over

dbSNP: rs4529890; hg19: chr11-128741080;