rs675482

Positions:

• chr11-128856699-A-G
• chr11-128856699-A-T

Variant summary

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

The NM_153766.3(KCNJ1):​c.-191-5809T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,964 control chromosomes in the GnomAD database, including 8,292 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 0.32 (8292 hom., cov: 32)
• Consequence: KCNJ1 NM_153766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ1	NM_153766.3	c.-191-5809T>C		intron_variant		ENST00000392666.6	NP_722450.1
KCNJ1	NM_153765.3	c.30+9824T>C		intron_variant			NP_722449.3
KCNJ1	NM_153764.3	c.-22+10474T>C		intron_variant			NP_722448.1
KCNJ1	NM_153767.4	c.-191-5809T>C		intron_variant			NP_722451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ1	ENST00000392666.6	c.-191-5809T>C		intron_variant		1	NM_153766.3	ENSP00000376434.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49305 AN: 151844 Hom.: 8280 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.325 AC: 49349 AN: 151964 Hom.: 8292 Cov.: 32 AF XY: 0.326 AC XY: 24248 AN XY: 74280

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.300

Alfa AF: 0.297 Hom.: 13765

Bravo AF: 0.325

Asia WGS AF: 0.355 AC: 1234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.071
DANN	Benign	0.23

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: rs675482; hg19: chr11-128726594;