rs2238009

Positions:

• chr11-128841142-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
KCNJ1	NM_153766.3	c.-21-878G>A		intron_variant		ENST00000392666.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ1	ENST00000392666.6	c.-21-878G>A		intron_variant		1	NM_153766.3	P1

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

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.220

Alfa AF: 0.159 Hom.: 3157

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2238009; hg19: chr11-128711037;