rs2835831

Variant names:

• chr21-37614931-T-C
• rs2835831
• NM_002240.5:c.*10228A>G

Variant summary

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

The NM_002240.5(KCNJ6):​c.*10228A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,076 control chromosomes in the GnomAD database, including 6,822 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 0.29 (6822 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: KCNJ6 NM_002240.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 4 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]

ENSG00000286717 (HGNC:):

KCNJ6-AS1 (HGNC:41352): (KCNJ6 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 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.*10228A>G		3_prime_UTR	Exon 4 of 4	NP_002231.1	P48051
	KCNJ6-AS1	NR_183540.1		n.408-83624T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.*10228A>G		3_prime_UTR	Exon 4 of 4	ENSP00000477437.1	P48051
	ENSG00000286717	ENST00000667151.1		n.160+20795T>C		intron	N/A
	ENSG00000286717	ENST00000838658.1		n.234+20795T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44512 AN: 151950 Hom.: 6812 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.293 AC: 44555 AN: 152070 Hom.: 6822 Cov.: 32 AF XY: 0.294 AC XY: 21855 AN XY: 74334

African (AFR) AF: 0.267 AC: 11083 AN: 41448

American (AMR) AF: 0.232 AC: 3541 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1068 AN: 3466

East Asian (EAS) AF: 0.138 AC: 717 AN: 5180

South Asian (SAS) AF: 0.335 AC: 1613 AN: 4816

European-Finnish (FIN) AF: 0.365 AC: 3860 AN: 10570

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21468 AN: 67988

Other (OTH) AF: 0.287 AC: 607 AN: 2114

Alfa AF: 0.312 Hom.: 10401

Bravo AF: 0.283

Asia WGS AF: 0.197 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		0.028
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: rs2835831; hg19: chr21-38987233;