rs3787870

Variant names:

• chr21-37913150-G-A
• rs3787870
• NM_002240.5:c.-28+2734C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-37913150-G-A
• chr21-37913150-G-T

Variant summary

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

The NM_002240.5(KCNJ6):​c.-28+2734C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,052 control chromosomes in the GnomAD database, including 29,420 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 0.61 (29420 hom., cov: 32)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 7 publications found

Genes affected

KCNJ6 (HGNC:6267): (potassium inwardly rectifying channel subfamily J member 6) This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability. [provided by RefSeq, Apr 2015]

KCNJ6 Gene-Disease associations (from GenCC):

• Keppen-Lubinsky syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002240.5. 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
	KCNJ6	NM_002240.5	MANE Select	c.-28+2734C>T		intron	N/A	NP_002231.1	P48051

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.-28+2734C>T		intron	N/A	ENSP00000477437.1	P48051
	KCNJ6	ENST00000645093.1		c.-27-72441C>T		intron	N/A	ENSP00000493772.1	P48051
	KCNJ6	ENST00000917423.1		c.-28+79C>T		intron	N/A	ENSP00000587482.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92941 AN: 151934 Hom.: 29386 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.612 AC: 93025 AN: 152052 Hom.: 29420 Cov.: 32 AF XY: 0.606 AC XY: 45010 AN XY: 74312

African (AFR) AF: 0.784 AC: 32505 AN: 41484

American (AMR) AF: 0.564 AC: 8613 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2008 AN: 3472

East Asian (EAS) AF: 0.460 AC: 2381 AN: 5180

South Asian (SAS) AF: 0.606 AC: 2919 AN: 4820

European-Finnish (FIN) AF: 0.463 AC: 4885 AN: 10550

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37562 AN: 67946

Other (OTH) AF: 0.601 AC: 1271 AN: 2114

Alfa AF: 0.574 Hom.: 46924

Bravo AF: 0.628

Asia WGS AF: 0.588 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.40
DANN	Benign	0.51
PhyloP100		-0.40
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: rs3787870; hg19: chr21-39285453;