rs147611594

Variant names:

• chr11-128842385-C-A
• rs147611594
• ENST00000392664.2:c.33G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-128842385-C-A
• chr11-128842385-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000220.6(KCNJ1):​c.33G>T​(p.Thr11Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T11T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNJ1 NM_000220.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0660
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 11-128842385-C-A is Benign according to our data. Variant chr11-128842385-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2781121.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.066 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000220.6. 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.-21-2121G>T		intron	N/A	NP_722450.1	P48048-2
	KCNJ1	NM_000220.6		c.33G>T	p.Thr11Thr	synonymous	Exon 1 of 2	NP_000211.1	P48048-1
	KCNJ1	NM_153765.3		c.31-2121G>T		intron	N/A	NP_722449.3	P48048-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ1	ENST00000392664.2	TSL:1	c.33G>T	p.Thr11Thr	synonymous	Exon 1 of 2	ENSP00000376432.2	P48048-1
	KCNJ1	ENST00000392666.6	TSL:1 MANE Select	c.-21-2121G>T		intron	N/A	ENSP00000376434.1	P48048-2
	KCNJ1	ENST00000324036.7	TSL:1	c.-21-2121G>T		intron	N/A	ENSP00000316233.3	P48048-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.0
DANN	Benign	0.53
PhyloP100		0.066
PromoterAI		0.016	Neutral

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: rs147611594; hg19: chr11-128712280;