rs347519

chr19-43769364-T-Cchr19-43769364-T-G

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.92

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=-0.7).
• 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNN4	NM_002250.3	c.1049+78A>G		intron_variant		ENST00000648319.1
KCNN4	XM_005258882.3	c.953+78A>G		intron_variant
KCNN4	XM_005258883.3	c.860+78A>G		intron_variant
KCNN4	XM_047438794.1	c.377+78A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNN4	ENST00000648319.1	c.1049+78A>G		intron_variant			NM_002250.3	P1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45818 AN: 151942 Hom.: 8026 Cov.: 32

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

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.: 13 AF XY: 0.223 AC XY: 115451 AN XY: 517146

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.: 32 AF XY: 0.296 AC XY: 22025 AN XY: 74324

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs347519; hg19: chr19-44273516; COSMIC: COSV53455435; COSMIC: COSV53455435;