rs2401756

chr14-88254564-G-Achr14-88254564-G-C

Variant summary

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

The NM_138317.3(KCNK10):c.402+8638C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,036 control chromosomes in the GnomAD database, including 34,450 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 0.67 (34450 hom., cov: 31)
• Consequence: KCNK10 NM_138317.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668

Genes affected

KCNK10 (HGNC:6273): (potassium two pore domain channel subfamily K member 10) The protein encoded by this gene belongs to the family of potassium channel proteins containing two pore-forming P domains. This channel is an open rectifier which primarily passes outward current under physiological K+ concentrations, and is stimulated strongly by arachidonic acid and to a lesser degree by membrane stretching, intracellular acidification, and general anaesthetics. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -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 = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK10	NM_138317.3	c.402+8638C>T		intron_variant		ENST00000319231.10
KCNK10	NM_021161.5	c.387+8638C>T		intron_variant
KCNK10	NM_138318.3	c.402+8638C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK10	ENST00000319231.10	c.402+8638C>T		intron_variant		1	NM_138317.3	P1
KCNK10	ENST00000312350.9	c.402+8638C>T		intron_variant		1
KCNK10	ENST00000340700.9	c.387+8638C>T		intron_variant		1
KCNK10	ENST00000556282.1	c.351+8638C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101503 AN: 151916 Hom.: 34403 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.668 AC: 101609 AN: 152036 Hom.: 34450 Cov.: 31 AF XY: 0.668 AC XY: 49643 AN XY: 74278

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.634

Alfa AF: 0.630 Hom.: 13897

Bravo AF: 0.673

Asia WGS AF: 0.704 AC: 2449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.66
Dann	Benign	0.78

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: rs2401756; hg19: chr14-88720908;