rs2306799

Variant names:

• chr19-43769889-G-A
• rs2306799
• NM_002250.3:c.820-60C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-43769889-G-A
• chr19-43769889-G-C
• chr19-43769889-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002250.3(KCNN4):​c.820-60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,173,166 control chromosomes in the GnomAD database, including 22,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3152 hom., cov: 31)
  • Exomes 𝑓: 0.19 (19594 hom.)
• Consequence: KCNN4 NM_002250.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.884
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-43769889-G-A is Benign according to our data. Variant chr19-43769889-G-A is described in ClinVar as Benign. ClinVar VariationId is 1283590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN4	NM_002250.3	c.820-60C>T		intron_variant	Intron 4 of 8	ENST00000648319.1	NP_002241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN4	ENST00000648319.1	c.820-60C>T		intron_variant	Intron 4 of 8		NM_002250.3	ENSP00000496939.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30650 AN: 151734 Hom.: 3155 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.193 AC: 196614 AN: 1021316 Hom.: 19594 AF XY: 0.192 AC XY: 100019 AN XY: 521680

African (AFR) AF: 0.211 AC: 5252 AN: 24858

American (AMR) AF: 0.106 AC: 4102 AN: 38572

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 4657 AN: 20432

East Asian (EAS) AF: 0.196 AC: 7362 AN: 37572

South Asian (SAS) AF: 0.157 AC: 11388 AN: 72442

European-Finnish (FIN) AF: 0.215 AC: 8553 AN: 39722

Middle Eastern (MID) AF: 0.195 AC: 915 AN: 4702

European-Non Finnish (NFE) AF: 0.197 AC: 145485 AN: 737316

Other (OTH) AF: 0.195 AC: 8900 AN: 45700

GnomAD4 genome AF: 0.202 AC: 30645 AN: 151850 Hom.: 3152 Cov.: 31 AF XY: 0.200 AC XY: 14825 AN XY: 74188

African (AFR) AF: 0.218 AC: 9011 AN: 41414

American (AMR) AF: 0.150 AC: 2283 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3472

East Asian (EAS) AF: 0.270 AC: 1388 AN: 5138

South Asian (SAS) AF: 0.155 AC: 745 AN: 4806

European-Finnish (FIN) AF: 0.219 AC: 2305 AN: 10536

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.197 AC: 13376 AN: 67920

Other (OTH) AF: 0.212 AC: 445 AN: 2100

Alfa AF: 0.132 Hom.: 362

Bravo AF: 0.199

Asia WGS AF: 0.201 AC: 697 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.29
DANN	Benign	0.64
PhyloP100		-0.88
PromoterAI		-0.00090	Neutral
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: rs2306799; hg19: chr19-44274041; COSMIC: COSV53456898; COSMIC: COSV53456898;