rs6448050

Variant names:

• chr4-21406136-C-T
• rs6448050
• NM_025221.6:c.62-523427G>A

Variant summary

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

The NM_025221.6(KCNIP4):​c.62-523427G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,022 control chromosomes in the GnomAD database, including 14,010 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 0.40 (14010 hom., cov: 33)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025221.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP4	NM_025221.6	MANE Select	c.62-523427G>A		intron	N/A	NP_079497.2
	KCNIP4	NM_001035003.2		c.88+291214G>A		intron	N/A	NP_001030175.1	Q6PIL6-5
	KCNIP4	NM_147181.4		c.61+542435G>A		intron	N/A	NP_671710.1	Q6PIL6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP4	ENST00000382152.7	TSL:5 MANE Select	c.62-523427G>A		intron	N/A	ENSP00000371587.2	Q6PIL6-1
	KCNIP4	ENST00000382148.7	TSL:1	c.88+291214G>A		intron	N/A	ENSP00000371583.3	Q6PIL6-5
	KCNIP4	ENST00000509207.1	TSL:1	c.-24+138254G>A		intron	N/A	ENSP00000423257.1	Q6PIL6-3

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61297 AN: 151906 Hom.: 14001 Cov.: 33

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.404 AC: 61359 AN: 152022 Hom.: 14010 Cov.: 33 AF XY: 0.399 AC XY: 29686 AN XY: 74316

African (AFR) AF: 0.632 AC: 26202 AN: 41478

American (AMR) AF: 0.366 AC: 5593 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1499 AN: 3470

East Asian (EAS) AF: 0.348 AC: 1798 AN: 5164

South Asian (SAS) AF: 0.263 AC: 1266 AN: 4822

European-Finnish (FIN) AF: 0.270 AC: 2852 AN: 10570

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20855 AN: 67936

Other (OTH) AF: 0.397 AC: 837 AN: 2110

Alfa AF: 0.338 Hom.: 38865

Bravo AF: 0.422

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.63
PhyloP100		-0.066
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: rs6448050; hg19: chr4-21407759;