rs2306801

Positions:

• chr19-43776326-G-A
• chr19-43776326-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.255+215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 151,304 control chromosomes in the GnomAD database, including 2,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2004 hom., cov: 28)
• Consequence: KCNN4 NM_002250.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.596

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=-0.9).
• BP6: Variant 19-43776326-G-A is Benign according to our data. Variant chr19-43776326-G-A is described in ClinVar as [Benign]. Clinvar id is 1234226.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN4	NM_002250.3	c.255+215C>T		intron_variant		ENST00000648319.1	NP_002241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN4	ENST00000648319.1	c.255+215C>T		intron_variant			NM_002250.3	ENSP00000496939	P1
KCNN4	ENST00000599720.5	c.160-4223C>T		intron_variant, NMD_transcript_variant		5		ENSP00000472513
KCNN4	ENST00000599107.1	n.286+215C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24017 AN: 151186 Hom.: 2002 Cov.: 28

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.159 AC: 24036 AN: 151304 Hom.: 2004 Cov.: 28 AF XY: 0.155 AC XY: 11452 AN XY: 73870

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.0978

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.152

Alfa AF: 0.171 Hom.: 2031

Bravo AF: 0.160

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	-0.90
CADD	Benign	0.019
DANN	Benign	0.57

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: rs2306801; hg19: chr19-44280478;