ENST00000923294.1:c.-3337C>T

Variant names:

• chr11-128874308-G-A
• rs948215
• ENST00000923294.1:c.-3337C>T

Variant summary

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

The ENST00000923294.1(KCNJ1):​c.-3337C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 151,902 control chromosomes in the GnomAD database, including 34,591 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 0.67 (34591 hom., cov: 30)
• Consequence: KCNJ1 ENST00000923294.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 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.-3337C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000593353.1
	KCNJ1	ENST00000923294.1		c.-3337C>T		5_prime_UTR	Exon 1 of 3	ENSP00000593353.1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101271 AN: 151784 Hom.: 34579 Cov.: 30

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.667 AC: 101319 AN: 151902 Hom.: 34591 Cov.: 30 AF XY: 0.673 AC XY: 49954 AN XY: 74258

African (AFR) AF: 0.518 AC: 21406 AN: 41364

American (AMR) AF: 0.782 AC: 11937 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2387 AN: 3470

East Asian (EAS) AF: 0.880 AC: 4546 AN: 5164

South Asian (SAS) AF: 0.590 AC: 2839 AN: 4810

European-Finnish (FIN) AF: 0.748 AC: 7908 AN: 10566

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.705 AC: 47900 AN: 67952

Other (OTH) AF: 0.696 AC: 1471 AN: 2112

Alfa AF: 0.696 Hom.: 60827

Bravo AF: 0.666

Asia WGS AF: 0.743 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.023
DANN	Benign	0.38
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs948215; hg19: chr11-128744203;