rs2604204

Variant names:

• chr11-128917535-G-T
• rs2604204
• NM_000890.5:c.*804G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-128917535-G-T
• chr11-128917535-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000890.5(KCNJ5):​c.*804G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,168 control chromosomes in the GnomAD database, including 41,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41963 hom., cov: 34)
  • Exomes 𝑓: 0.72 (46 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNJ5 NM_000890.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.163
• Publications: 12 publications found

Genes affected

KCNJ5 (HGNC:6266): (potassium inwardly rectifying channel subfamily J member 5) This gene encodes an integral membrane protein which belongs to one of seven subfamilies of inward-rectifier potassium channel proteins called potassium channel subfamily J. The encoded protein is a subunit of the potassium channel which is homotetrameric. It is controlled by G-proteins and has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Naturally occurring mutations in this gene are associated with aldosterone-producing adenomas. [provided by RefSeq, Aug 2017]

KCNJ5 Gene-Disease associations (from GenCC):

• familial hyperaldosteronism type III

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
• Andersen-Tawil syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• long QT syndrome 13

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• long QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-128917535-G-T is Benign according to our data. Variant chr11-128917535-G-T is described in ClinVar as Benign. ClinVar VariationId is 303649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000890.5. 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
	KCNJ5	NM_000890.5	MANE Select	c.*804G>T		3_prime_UTR	Exon 3 of 3	NP_000881.3
	KCNJ5	NM_001354169.2		c.*804G>T		3_prime_UTR	Exon 4 of 4	NP_001341098.1	P48544

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ5	ENST00000529694.6	TSL:1 MANE Select	c.*804G>T		3_prime_UTR	Exon 3 of 3	ENSP00000433295.1	P48544
	KCNJ5	ENST00000904658.1		c.*804G>T		3_prime_UTR	Exon 4 of 4	ENSP00000574717.1
	KCNJ5	ENST00000957736.1		c.*804G>T		3_prime_UTR	Exon 3 of 3	ENSP00000627795.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112674 AN: 152050 Hom.: 41932 Cov.: 34

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.773

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.719 AC: 128 AN: 178 Hom.: 46 Cov.: 0 AF XY: 0.714 AC XY: 90 AN XY: 126

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 3 AN: 6

South Asian (SAS) AF: 0.500 AC: 2 AN: 4

European-Finnish (FIN) AF: 0.750 AC: 6 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.713 AC: 107 AN: 150

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.741 AC: 112764 AN: 152168 Hom.: 41963 Cov.: 34 AF XY: 0.741 AC XY: 55138 AN XY: 74390

African (AFR) AF: 0.784 AC: 32557 AN: 41528

American (AMR) AF: 0.740 AC: 11321 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2621 AN: 3470

East Asian (EAS) AF: 0.669 AC: 3441 AN: 5144

South Asian (SAS) AF: 0.770 AC: 3716 AN: 4824

European-Finnish (FIN) AF: 0.681 AC: 7197 AN: 10564

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49332 AN: 68022

Other (OTH) AF: 0.774 AC: 1637 AN: 2114

Alfa AF: 0.714 Hom.: 6307

Bravo AF: 0.745

Asia WGS AF: 0.746 AC: 2588 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital long QT syndrome (1)
-	-	1	Familial hyperaldosteronism type III (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		-0.16
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: rs2604204; hg19: chr11-128787430;