8-139639536-G-A

Position:

• chr8-139639536-G-A

Variant summary

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

The NM_001282534.2(KCNK9):​c.284-20437C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,212 control chromosomes in the GnomAD database, including 2,784 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 0.18 (2784 hom., cov: 34)
• Consequence: KCNK9 NM_001282534.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

Genes affected

KCNK9 (HGNC:6283): (potassium two pore domain channel subfamily K member 9) This gene encodes a protein that contains multiple transmembrane regions and two pore-forming P domains and functions as a pH-dependent potassium channel. Amplification and overexpression of this gene have been observed in several types of human carcinomas. This gene is imprinted in the brain, with preferential expression from the maternal allele. A mutation in this gene was associated with Birk-Barel dysmorphism syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK9	NM_001282534.2	c.284-20437C>T		intron_variant		ENST00000520439.3	NP_001269463.1
KCNK9	NR_104210.2	n.415-20437C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK9	ENST00000520439.3	c.284-20437C>T		intron_variant		1	NM_001282534.2	ENSP00000430676	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28124 AN: 152094 Hom.: 2774 Cov.: 34

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.185 AC: 28147 AN: 152212 Hom.: 2784 Cov.: 34 AF XY: 0.191 AC XY: 14188 AN XY: 74404

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.158

Alfa AF: 0.169 Hom.: 1946

Bravo AF: 0.169

Asia WGS AF: 0.243 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.69
DANN	Benign	0.57

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: rs1469039; hg19: chr8-140651779;