11-128857106-T-C

Variant names:

• chr11-128857106-T-C
• rs673614
• NM_153766.3:c.-191-6216A>G

Variant summary

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

The NM_153766.3(KCNJ1):​c.-191-6216A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,946 control chromosomes in the GnomAD database, including 12,704 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 0.38 (12704 hom., cov: 32)
• Consequence: KCNJ1 NM_153766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 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.-191-6216A>G		intron	N/A	NP_722450.1
	KCNJ1	NM_153765.3		c.30+9417A>G		intron	N/A	NP_722449.3
	KCNJ1	NM_153764.3		c.-22+10067A>G		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.-191-6216A>G		intron	N/A	ENSP00000376434.1
	KCNJ1	ENST00000324036.7	TSL:1	c.-191-6216A>G		intron	N/A	ENSP00000316233.3
	KCNJ1	ENST00000392665.6	TSL:1	c.-22+10067A>G		intron	N/A	ENSP00000376433.2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58188 AN: 151828 Hom.: 12679 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.383 AC: 58255 AN: 151946 Hom.: 12704 Cov.: 32 AF XY: 0.383 AC XY: 28477 AN XY: 74260

African (AFR) AF: 0.600 AC: 24859 AN: 41398

American (AMR) AF: 0.273 AC: 4177 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3464

East Asian (EAS) AF: 0.405 AC: 2088 AN: 5156

South Asian (SAS) AF: 0.393 AC: 1889 AN: 4810

European-Finnish (FIN) AF: 0.344 AC: 3624 AN: 10550

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19722 AN: 67966

Other (OTH) AF: 0.342 AC: 720 AN: 2108

Alfa AF: 0.235 Hom.: 740

Bravo AF: 0.392

Asia WGS AF: 0.371 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.18
DANN	Benign	0.42
PhyloP100		-0.65
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: rs673614; hg19: chr11-128727001;