rs113008742

Variant names:

• chr11-128838623-C-CTTG
• rs113008742
• NM_153766.3:c.*499_*501dupCAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_153766.3(KCNJ1):​c.*499_*501dupCAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 160,464 control chromosomes in the GnomAD database, including 2,142 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2033 hom., cov: 29)
  • Exomes 𝑓: 0.13 (109 hom.)
• Consequence: KCNJ1 NM_153766.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49
• Publications: 2 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• antenatal Bartter syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-128838623-C-CTTG is Benign according to our data. Variant chr11-128838623-C-CTTG is described in ClinVar as Benign. ClinVar VariationId is 303561.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.29 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ1	NM_153766.3	MANE Select	c.*499_*501dupCAA		3_prime_UTR	Exon 3 of 3	NP_722450.1	P48048-2
	KCNJ1	NM_000220.6		c.*499_*501dupCAA		3_prime_UTR	Exon 2 of 2	NP_000211.1	P48048-1
	KCNJ1	NM_153765.3		c.*499_*501dupCAA		3_prime_UTR	Exon 3 of 3	NP_722449.3	P48048-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ1	ENST00000392666.6	TSL:1 MANE Select	c.*499_*501dupCAA		3_prime_UTR	Exon 3 of 3	ENSP00000376434.1	P48048-2
	KCNJ1	ENST00000324036.7	TSL:1	c.*499_*501dupCAA		3_prime_UTR	Exon 4 of 4	ENSP00000316233.3	P48048-2
	KCNJ1	ENST00000392665.6	TSL:1	c.*499_*501dupCAA		3_prime_UTR	Exon 2 of 2	ENSP00000376433.2	P48048-2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24429 AN: 151958 Hom.: 2025 Cov.: 29

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.127 AC: 1067 AN: 8388 Hom.: 109 Cov.: 0 AF XY: 0.131 AC XY: 593 AN XY: 4514

African (AFR) AF: 0.176 AC: 6 AN: 34

American (AMR) AF: 0.0729 AC: 87 AN: 1194

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 3 AN: 52

East Asian (EAS) AF: 0.0424 AC: 10 AN: 236

South Asian (SAS) AF: 0.251 AC: 208 AN: 828

European-Finnish (FIN) AF: 0.0721 AC: 15 AN: 208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 16

European-Non Finnish (NFE) AF: 0.125 AC: 680 AN: 5428

Other (OTH) AF: 0.148 AC: 58 AN: 392

GnomAD4 genome AF: 0.161 AC: 24457 AN: 152076 Hom.: 2033 Cov.: 29 AF XY: 0.164 AC XY: 12156 AN XY: 74332

African (AFR) AF: 0.185 AC: 7669 AN: 41492

American (AMR) AF: 0.101 AC: 1549 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3468

East Asian (EAS) AF: 0.102 AC: 528 AN: 5170

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4810

European-Finnish (FIN) AF: 0.198 AC: 2089 AN: 10566

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10242 AN: 67970

Other (OTH) AF: 0.149 AC: 314 AN: 2114

Alfa AF: 0.153 Hom.: 176

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Antenatal Bartter syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs113008742; hg19: chr11-128708518; COSMIC: COSV60661909; COSMIC: COSV60661909;