rs881333

Variant names:

• chr11-128870788-C-G
• rs881333
• ENST00000923294.1:c.-22+21G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-128870788-C-G
• chr11-128870788-C-T

Variant summary

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

The ENST00000923294.1(KCNJ1):​c.-22+21G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,070 control chromosomes in the GnomAD database, including 38,430 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 0.71 (38430 hom., cov: 31)
• Consequence: KCNJ1 ENST00000923294.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 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.-22+21G>C		intron	N/A	ENSP00000593353.1
	KCNJ1	ENST00000923295.1		c.-22+21G>C		intron	N/A	ENSP00000593354.1
	KCNJ1	ENST00000923296.1		c.-192+21G>C		intron	N/A	ENSP00000593355.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107796 AN: 151952 Hom.: 38389 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.709 AC: 107882 AN: 152070 Hom.: 38430 Cov.: 31 AF XY: 0.714 AC XY: 53064 AN XY: 74338

African (AFR) AF: 0.668 AC: 27735 AN: 41492

American (AMR) AF: 0.776 AC: 11862 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2500 AN: 3468

East Asian (EAS) AF: 0.827 AC: 4259 AN: 5152

South Asian (SAS) AF: 0.634 AC: 3054 AN: 4820

European-Finnish (FIN) AF: 0.742 AC: 7850 AN: 10580

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48201 AN: 67962

Other (OTH) AF: 0.708 AC: 1489 AN: 2102

Alfa AF: 0.668 Hom.: 2274

Bravo AF: 0.709

Asia WGS AF: 0.742 AC: 2581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.46
PhyloP100		0.16

Splicing

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

Other links and lift over

dbSNP: rs881333; hg19: chr11-128740683;