rs11942476

Positions:

• chr4-21453634-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025221.6(KCNIP4):​c.61+494937G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,128 control chromosomes in the GnomAD database, including 1,220 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 0.12 (1220 hom., cov: 32)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

Genes affected

KCNIP4 (HGNC:30083): (potassium voltage-gated channel interacting protein 4) This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the recoverin branch of the EF-hand superfamily. Members of the KCNIP family are small calcium binding proteins. They all have EF-hand-like domains, and differ from each other in the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. This protein member also interacts with presenilin. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.61+494937G>C		intron_variant		ENST00000382152.7	NP_079497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNIP4	ENST00000382152.7	c.61+494937G>C		intron_variant		5	NM_025221.6	ENSP00000371587

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17705 AN: 152010 Hom.: 1217 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0901

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.116 AC: 17716 AN: 152128 Hom.: 1220 Cov.: 32 AF XY: 0.113 AC XY: 8431 AN XY: 74362

Gnomad4 AFR AF: 0.0732

Gnomad4 AMR AF: 0.0900

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.000776

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.120

Alfa AF: 0.141 Hom.: 199

Bravo AF: 0.110

Asia WGS AF: 0.0680 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11942476; hg19: chr4-21455257;