rs2306799

Positions:

• chr19-43769889-G-A
• chr19-43769889-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002250.3(KCNN4):​c.820-60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,173,166 control chromosomes in the GnomAD database, including 22,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3152 hom., cov: 31)
  • Exomes 𝑓: 0.19 (19594 hom.)
• Consequence: KCNN4 NM_002250.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.884

Genes affected

KCNN4 (HGNC:6293): (potassium calcium-activated channel subfamily N member 4) The protein encoded by this gene is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization, which promotes calcium influx. The encoded protein may be part of the predominant calcium-activated potassium channel in T-lymphocytes. This gene is similar to other KCNN family potassium channel genes, but it differs enough to possibly be considered as part of a new subfamily. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-43769889-G-A is Benign according to our data. Variant chr19-43769889-G-A is described in ClinVar as [Benign]. Clinvar id is 1283590.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNN4	NM_002250.3	c.820-60C>T		intron_variant		ENST00000648319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNN4	ENST00000648319.1	c.820-60C>T		intron_variant			NM_002250.3	P1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30650 AN: 151734 Hom.: 3155 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.193 AC: 196614 AN: 1021316 Hom.: 19594 AF XY: 0.192 AC XY: 100019 AN XY: 521680

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.202 AC: 30645 AN: 151850 Hom.: 3152 Cov.: 31 AF XY: 0.200 AC XY: 14825 AN XY: 74188

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.212

Alfa AF: 0.132 Hom.: 362

Bravo AF: 0.199

Asia WGS AF: 0.201 AC: 697 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.29
DANN	Benign	0.64

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: rs2306799; hg19: chr19-44274041; COSMIC: COSV53456898; COSMIC: COSV53456898;