11-128863066-G-T

Variant names:

• chr11-128863066-G-T
• rs2855798
• NM_153766.3:c.-192+4107C>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.-192+4107C>A variant causes a intron change. The variant allele was found at a frequency of 0.212 in 152,158 control chromosomes in the GnomAD database, including 3,692 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 0.21 (3692 hom., cov: 33)
• Consequence: KCNJ1 NM_153766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• 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: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• antenatal Bartter syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC107984409 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153766.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ1	NM_153766.3	MANE Select	c.-192+4107C>A		intron	N/A	NP_722450.1
	KCNJ1	NM_153765.3		c.30+3457C>A		intron	N/A	NP_722449.3
	KCNJ1	NM_153764.3		c.-22+4107C>A		intron	N/A	NP_722448.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ1	ENST00000392666.6	TSL:1 MANE Select	c.-192+4107C>A		intron	N/A	ENSP00000376434.1
	KCNJ1	ENST00000324036.7	TSL:1	c.-192+3457C>A		intron	N/A	ENSP00000316233.3
	KCNJ1	ENST00000392665.6	TSL:1	c.-22+4107C>A		intron	N/A	ENSP00000376433.2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32209 AN: 152040 Hom.: 3678 Cov.: 33

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.212 AC: 32278 AN: 152158 Hom.: 3692 Cov.: 33 AF XY: 0.211 AC XY: 15667 AN XY: 74402

African (AFR) AF: 0.300 AC: 12460 AN: 41502

American (AMR) AF: 0.149 AC: 2271 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3470

East Asian (EAS) AF: 0.115 AC: 598 AN: 5178

South Asian (SAS) AF: 0.314 AC: 1515 AN: 4824

European-Finnish (FIN) AF: 0.177 AC: 1878 AN: 10588

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12494 AN: 67988

Other (OTH) AF: 0.201 AC: 425 AN: 2116

Alfa AF: 0.191 Hom.: 4461

Bravo AF: 0.212

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.77
PhyloP100		3.8
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: rs2855798; hg19: chr11-128732961;