rs1495509

Variant names:

• chr4-21391993-T-C
• rs1495509
• NM_025221.6:c.62-509284A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-21391993-T-C
• chr4-21391993-T-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.62-509284A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,104 control chromosomes in the GnomAD database, including 6,631 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 0.27 (6631 hom., cov: 32)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.62-509284A>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.62-509284A>G		intron_variant	Intron 1 of 8	5	NM_025221.6	ENSP00000371587.2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41809 AN: 151986 Hom.: 6626 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.275 AC: 41827 AN: 152104 Hom.: 6631 Cov.: 32 AF XY: 0.281 AC XY: 20862 AN XY: 74346

African (AFR) AF: 0.125 AC: 5189 AN: 41526

American (AMR) AF: 0.248 AC: 3782 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 890 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2080 AN: 5154

South Asian (SAS) AF: 0.402 AC: 1938 AN: 4822

European-Finnish (FIN) AF: 0.427 AC: 4525 AN: 10592

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22452 AN: 67962

Other (OTH) AF: 0.258 AC: 544 AN: 2112

Alfa AF: 0.308 Hom.: 31834

Bravo AF: 0.251

Asia WGS AF: 0.371 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.74
PhyloP100		-0.12
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: rs1495509; hg19: chr4-21393616; COSMIC: COSV66179787;