rs2306801

Variant names:

• chr19-43776326-G-A
• rs2306801
• NM_002250.3:c.255+215C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-43776326-G-A
• chr19-43776326-G-C
• chr19-43776326-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002250.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNN4	NM_002250.3	MANE Select	c.255+215C>T		intron	N/A	NP_002241.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNN4	ENST00000648319.1	MANE Select	c.255+215C>T		intron	N/A	ENSP00000496939.1
	KCNN4	ENST00000599107.1	TSL:2	n.286+215C>T		intron	N/A
	KCNN4	ENST00000599720.5	TSL:5	n.160-4223C>T		intron	N/A	ENSP00000472513.1

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

African (AFR) AF: 0.135 AC: 5556 AN: 41132

American (AMR) AF: 0.136 AC: 2065 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 581 AN: 3466

East Asian (EAS) AF: 0.154 AC: 783 AN: 5088

South Asian (SAS) AF: 0.186 AC: 886 AN: 4776

European-Finnish (FIN) AF: 0.0978 AC: 1026 AN: 10490

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12627 AN: 67854

Other (OTH) AF: 0.152 AC: 318 AN: 2098

Alfa AF: 0.172 Hom.: 2450

Bravo AF: 0.160

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.019
DANN	Benign	0.57
PhyloP100		-0.60
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: rs2306801; hg19: chr19-44280478;