19-43777410-T-C

Variant names:

• chr19-43777410-T-C
• rs670950
• NM_002250.3:c.160-774A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002250.3(KCNN4):​c.160-774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 151,030 control chromosomes in the GnomAD database, including 57,625 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 0.87 (57625 hom., cov: 25)
• Consequence: KCNN4 NM_002250.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• dehydrated hereditary stomatocytosis 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• dehydrated hereditary stomatocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN4	NM_002250.3	c.160-774A>G		intron_variant	Intron 1 of 8	ENST00000648319.1	NP_002241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN4	ENST00000648319.1	c.160-774A>G		intron_variant	Intron 1 of 8		NM_002250.3	ENSP00000496939.1
KCNN4	ENST00000599720.5	n.159+3293A>G		intron_variant	Intron 1 of 6	5		ENSP00000472513.1

Frequencies

GnomAD3 genomes AF: 0.870 AC: 131342 AN: 150910 Hom.: 57591 Cov.: 25

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.966

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.870 AC: 131427 AN: 151030 Hom.: 57625 Cov.: 25 AF XY: 0.872 AC XY: 64316 AN XY: 73720

African (AFR) AF: 0.751 AC: 30749 AN: 40922

American (AMR) AF: 0.908 AC: 13766 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.966 AC: 3353 AN: 3470

East Asian (EAS) AF: 0.917 AC: 4680 AN: 5104

South Asian (SAS) AF: 0.923 AC: 4435 AN: 4804

European-Finnish (FIN) AF: 0.914 AC: 9497 AN: 10396

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.913 AC: 61981 AN: 67884

Other (OTH) AF: 0.869 AC: 1813 AN: 2086

Alfa AF: 0.901 Hom.: 186846

Bravo AF: 0.866

Asia WGS AF: 0.875 AC: 3043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.68
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs670950; hg19: chr19-44281562;