Variant 19-43769364-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002250.3(KCNN4):c.1049+78A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,160,372 control chromosomes in the GnomAD database, including 35,414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8043 hom., cov: 32)

Exomes 𝑓: 0.22 ( 27371 hom. )

Consequence

KCNN4
NM_002250.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.92

Variant links:

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 links:

KCNN4 (HGNC:):

KCNN4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 19-43769364-T-C is Benign according to our data. Variant chr19-43769364-T-C is described in ClinVar as [Benign]. Clinvar id is 1260319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
KCNN4	NM_002250.3 linkuse as main transcript	c.1049+78A>G	intron_variant	ENST00000648319.1	NP_002241.1
KCNN4	XM_005258882.3 linkuse as main transcript	c.953+78A>G	intron_variant		XP_005258939.1
KCNN4	XM_005258883.3 linkuse as main transcript	c.860+78A>G	intron_variant		XP_005258940.1
KCNN4	XM_047438794.1 linkuse as main transcript	c.377+78A>G	intron_variant		XP_047294750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN4	ENST00000648319.1 linkuse as main transcript	c.1049+78A>G		intron_variant			NM_002250.3	ENSP00000496939.1		O15554

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45818

AN:

151942

Hom.:

8026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.301

GnomAD3 exomes

AF:

0.235

AC:

54485

AN:

231728

Hom.:

7352

AF XY:

0.232

AC XY:

29076

AN XY:

125148

show subpopulations

Gnomad AFR exome

AF:

0.503

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.281

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.232

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.225

AC:

226560

AN:

1008312

Hom.:

27371

Cov.:

AF XY:

0.223

AC XY:

115451

AN XY:

517146

show subpopulations

Gnomad4 AFR exome

AF:

0.497

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.275

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.223

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.302

AC:

45868

AN:

152060

Hom.:

8043

Cov.:

AF XY:

0.296

AC XY:

22025

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.497

Gnomad4 AMR

AF:

0.202

Gnomad4 ASJ

AF:

0.262

Gnomad4 EAS

AF:

0.273

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.233

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.298

Alfa

AF:

0.193

Hom.:

591

Bravo

AF:

0.309

Asia WGS

AF:

0.231

AC:

802

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 25179167) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.45

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over