rs1148058

chr11-128842886-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153766.3(KCNJ1):c.-21-2622C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,168 control chromosomes in the GnomAD database, including 2,303 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 0.16 (2303 hom., cov: 33)
• Consequence: KCNJ1 NM_153766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ1	NM_153766.3	c.-21-2622C>T		intron_variant		ENST00000392666.6
KCNJ1	NM_153764.3	c.-21-2622C>T		intron_variant
KCNJ1	NM_153765.3	c.31-2622C>T		intron_variant
KCNJ1	NM_153767.4	c.-21-2622C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ1	ENST00000392666.6	c.-21-2622C>T		intron_variant		1	NM_153766.3	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24846 AN: 152048 Hom.: 2303 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.163 AC: 24851 AN: 152168 Hom.: 2303 Cov.: 33 AF XY: 0.167 AC XY: 12460 AN XY: 74390

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.167

Alfa AF: 0.169 Hom.: 3818

Bravo AF: 0.159

Asia WGS AF: 0.209 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.92
Dann	Benign	0.27

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: rs1148058; hg19: chr11-128712781;