rs17520130

Variant names:

• chr4-21322568-T-C
• rs17520130
• NM_025221.6:c.62-439859A>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.62-439859A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,898 control chromosomes in the GnomAD database, including 17,459 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 0.47 (17459 hom., cov: 31)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.62-439859A>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.62-439859A>G		intron_variant	Intron 1 of 8	5	NM_025221.6	ENSP00000371587.2

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71709 AN: 151780 Hom.: 17447 Cov.: 31

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.472 AC: 71755 AN: 151898 Hom.: 17459 Cov.: 31 AF XY: 0.471 AC XY: 34957 AN XY: 74206

African (AFR) AF: 0.593 AC: 24568 AN: 41458

American (AMR) AF: 0.440 AC: 6704 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2029 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2253 AN: 5168

South Asian (SAS) AF: 0.464 AC: 2226 AN: 4802

European-Finnish (FIN) AF: 0.429 AC: 4515 AN: 10532

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28035 AN: 67920

Other (OTH) AF: 0.465 AC: 976 AN: 2098

Alfa AF: 0.444 Hom.: 47405

Bravo AF: 0.477

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.54
PhyloP100		-1.2
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: rs17520130; hg19: chr4-21324191;