rs6448050

Positions:

• chr4-21406136-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNIP4	NM_025221.6	c.62-523427G>A		intron_variant		ENST00000382152.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNIP4	ENST00000382152.7	c.62-523427G>A		intron_variant		5	NM_025221.6

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

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.397

Alfa AF: 0.325 Hom.: 16777

Bravo AF: 0.422

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6448050; hg19: chr4-21407759;