rs2238009

Variant names:

• chr11-128841142-C-T
• rs2238009
• NM_153766.3:c.-21-878G>A

Variant summary

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

The NM_153766.3(KCNJ1):​c.-21-878G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,060 control chromosomes in the GnomAD database, including 7,288 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 0.26 (7288 hom., cov: 32)
• Consequence: KCNJ1 NM_153766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 5 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: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• 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 = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ1	NM_153766.3	c.-21-878G>A		intron_variant	Intron 2 of 2	ENST00000392666.6	NP_722450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ1	ENST00000392666.6	c.-21-878G>A		intron_variant	Intron 2 of 2	1	NM_153766.3	ENSP00000376434.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39075 AN: 151942 Hom.: 7263 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.257 AC: 39144 AN: 152060 Hom.: 7288 Cov.: 32 AF XY: 0.255 AC XY: 18937 AN XY: 74362

African (AFR) AF: 0.528 AC: 21893 AN: 41442

American (AMR) AF: 0.183 AC: 2800 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3464

East Asian (EAS) AF: 0.300 AC: 1550 AN: 5174

South Asian (SAS) AF: 0.124 AC: 598 AN: 4812

European-Finnish (FIN) AF: 0.151 AC: 1597 AN: 10586

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9480 AN: 67986

Other (OTH) AF: 0.220 AC: 464 AN: 2108

Alfa AF: 0.171 Hom.: 4857

Bravo AF: 0.277

Asia WGS AF: 0.205 AC: 714 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	1.2
DANN	Benign	0.45
PhyloP100		-0.010
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: rs2238009; hg19: chr11-128711037;