chr21-37618141-G-A

Position:

• chr21-37618141-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002240.5(KCNJ6):​c.*7018C>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 0.294 in 152,222 control chromosomes in the GnomAD database, including 6,908 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 (6903 hom., cov: 33)
  • Exomes 𝑓: 0.30 (5 hom.)
• Consequence: KCNJ6 NM_002240.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ6	NM_002240.5	c.*7018C>T		3_prime_UTR_variant	4/4	ENST00000609713.2
KCNJ6-AS1	NR_183540.1	n.408-80414G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ6	ENST00000609713.2	c.*7018C>T		3_prime_UTR_variant	4/4	1	NM_002240.5	P1
	ENST00000667151.1	n.160+24005G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44724 AN: 152034 Hom.: 6893 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.300 AC: 21 AN: 70 Hom.: 5 Cov.: 0 AF XY: 0.308 AC XY: 16 AN XY: 52

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.323

GnomAD4 genome AF: 0.294 AC: 44767 AN: 152152 Hom.: 6903 Cov.: 33 AF XY: 0.295 AC XY: 21974 AN XY: 74392

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.291

Alfa AF: 0.315 Hom.: 7690

Bravo AF: 0.284

Asia WGS AF: 0.197 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2835837; hg19: chr21-38990443;