19-43768194-A-G

Position:

• chr19-43768194-A-G

Variant summary

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

The NM_002250.3(KCNN4):​c.1120-487T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,082 control chromosomes in the GnomAD database, including 6,361 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 0.28 (6361 hom., cov: 33)
• Consequence: KCNN4 NM_002250.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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]

KCNN4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN4	NM_002250.3	c.1120-487T>C		intron_variant		ENST00000648319.1	NP_002241.1
KCNN4	XM_005258882.3	c.1024-487T>C		intron_variant			XP_005258939.1
KCNN4	XM_005258883.3	c.931-487T>C		intron_variant			XP_005258940.1
KCNN4	XM_047438794.1	c.448-487T>C		intron_variant			XP_047294750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN4	ENST00000648319.1	c.1120-487T>C		intron_variant			NM_002250.3	ENSP00000496939.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 42011 AN: 151964 Hom.: 6353 Cov.: 33

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.276 AC: 42039 AN: 152082 Hom.: 6361 Cov.: 33 AF XY: 0.272 AC XY: 20241 AN XY: 74364

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.283

Alfa AF: 0.199 Hom.: 790

Bravo AF: 0.281

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.11
DANN	Benign	0.42

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: rs3786954; hg19: chr19-44272346;