chr4-21331788-T-C

Variant names:

• chr4-21331788-T-C
• rs1364836
• NM_025221.6:c.62-449079A>G

Variant summary

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

The NM_025221.6(KCNIP4):​c.62-449079A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 151,982 control chromosomes in the GnomAD database, including 41,184 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 0.73 (41184 hom., cov: 32)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 3 publications found

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]

ENSG00000250243 (HGNC:41254):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.62-449079A>G		intron_variant	Intron 1 of 8	ENST00000382152.7	NP_079497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNIP4	ENST00000382152.7	c.62-449079A>G		intron_variant	Intron 1 of 8	5	NM_025221.6	ENSP00000371587.2

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110820 AN: 151864 Hom.: 41142 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.730 AC: 110915 AN: 151982 Hom.: 41184 Cov.: 32 AF XY: 0.729 AC XY: 54108 AN XY: 74262

African (AFR) AF: 0.878 AC: 36424 AN: 41506

American (AMR) AF: 0.740 AC: 11280 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2777 AN: 3470

East Asian (EAS) AF: 0.620 AC: 3190 AN: 5148

South Asian (SAS) AF: 0.689 AC: 3322 AN: 4822

European-Finnish (FIN) AF: 0.660 AC: 6973 AN: 10562

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44652 AN: 67910

Other (OTH) AF: 0.738 AC: 1556 AN: 2108

Alfa AF: 0.691 Hom.: 67339

Bravo AF: 0.742

Asia WGS AF: 0.711 AC: 2472 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.9
DANN	Benign	0.62
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1364836; hg19: chr4-21333411;