8-139639536-G-A

Variant names:

• chr8-139639536-G-A
• rs1469039
• NM_001282534.2:c.284-20437C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

KCNK9 Gene-Disease associations (from GenCC):

• Birk-Barel syndrome

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282534.2. 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
	KCNK9	NM_001282534.2	MANE Select	c.284-20437C>T		intron	N/A	NP_001269463.1
	KCNK9	NR_104210.2		n.415-20437C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK9	ENST00000520439.3	TSL:1 MANE Select	c.284-20437C>T		intron	N/A	ENSP00000430676.1
	KCNK9	ENST00000303015.2	TSL:1	c.284-20437C>T		intron	N/A	ENSP00000302166.1
	KCNK9	ENST00000648164.1		c.284-20437C>T		intron	N/A	ENSP00000498198.1

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

African (AFR) AF: 0.198 AC: 8245 AN: 41540

American (AMR) AF: 0.109 AC: 1668 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1478 AN: 5166

South Asian (SAS) AF: 0.254 AC: 1225 AN: 4824

European-Finnish (FIN) AF: 0.287 AC: 3044 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11610 AN: 67994

Other (OTH) AF: 0.158 AC: 333 AN: 2110

Alfa AF: 0.172 Hom.: 5558

Bravo AF: 0.169

Asia WGS AF: 0.243 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.69
DANN	Benign	0.57
PhyloP100		-1.9
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: rs1469039; hg19: chr8-140651779;