rs4937391

Variant names:

• chr11-128916399-G-A
• rs4937391
• NM_000890.5:c.938-10G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-128916399-G-A
• chr11-128916399-G-C

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.938-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 1,608,824 control chromosomes in the GnomAD database, including 423,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42221 hom., cov: 32)
  • Exomes 𝑓: 0.72 (381386 hom.)
• Consequence: KCNJ5 NM_000890.5 intron
• Scores: Splicing: ADA: 0.00004011
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.677
• Publications: 21 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, Labcorp Genetics (formerly Invitae)
• Andersen-Tawil syndrome

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

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.85).
• BP6: Variant 11-128916399-G-A is Benign according to our data. Variant chr11-128916399-G-A is described in ClinVar as Benign. ClinVar VariationId is 137995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ5	NM_000890.5	MANE Select	c.938-10G>A		intron	N/A	NP_000881.3
	KCNJ5	NM_001354169.2		c.938-10G>A		intron	N/A	NP_001341098.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ5	ENST00000529694.6	TSL:1 MANE Select	c.938-10G>A		intron	N/A	ENSP00000433295.1
	KCNJ5	ENST00000338350.4	TSL:1	c.938-10G>A		intron	N/A	ENSP00000339960.4
	KCNJ5	ENST00000533599.1	TSL:1	c.938-10G>A		intron	N/A	ENSP00000434266.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112980 AN: 152026 Hom.: 42202 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.771

GnomAD2 exomes AF: 0.731 AC: 183011 AN: 250316 AF XY: 0.734

Gnomad AFR exome AF: 0.794

Gnomad AMR exome AF: 0.710

Gnomad ASJ exome AF: 0.763

Gnomad EAS exome AF: 0.664

Gnomad FIN exome AF: 0.684

Gnomad NFE exome AF: 0.732

Gnomad OTH exome AF: 0.745

GnomAD4 exome AF: 0.723 AC: 1052544 AN: 1456680 Hom.: 381386 Cov.: 34 AF XY: 0.726 AC XY: 526065 AN XY: 725010

African (AFR) AF: 0.800 AC: 26723 AN: 33398

American (AMR) AF: 0.710 AC: 31730 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 19915 AN: 26112

East Asian (EAS) AF: 0.669 AC: 26540 AN: 39672

South Asian (SAS) AF: 0.778 AC: 67034 AN: 86180

European-Finnish (FIN) AF: 0.684 AC: 36527 AN: 53404

Middle Eastern (MID) AF: 0.809 AC: 4660 AN: 5762

European-Non Finnish (NFE) AF: 0.718 AC: 795428 AN: 1107198

Other (OTH) AF: 0.730 AC: 43987 AN: 60244

GnomAD4 genome AF: 0.743 AC: 113049 AN: 152144 Hom.: 42221 Cov.: 32 AF XY: 0.742 AC XY: 55187 AN XY: 74360

African (AFR) AF: 0.791 AC: 32813 AN: 41494

American (AMR) AF: 0.743 AC: 11361 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2615 AN: 3470

East Asian (EAS) AF: 0.660 AC: 3414 AN: 5170

South Asian (SAS) AF: 0.772 AC: 3719 AN: 4820

European-Finnish (FIN) AF: 0.682 AC: 7212 AN: 10582

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49339 AN: 67990

Other (OTH) AF: 0.772 AC: 1634 AN: 2116

Alfa AF: 0.737 Hom.: 22602

Bravo AF: 0.747

Asia WGS AF: 0.746 AC: 2590 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	Familial hyperaldosteronism type III (2)
-	-	1	Congenital long QT syndrome (1)
-	-	1	Long QT syndrome (1)
-	-	1	Long QT syndrome 13 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.41
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000040
dbscSNV1_RF	Benign	0.0020
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: rs4937391; hg19: chr11-128786294; COSMIC: COSV107435323;