4-21331788-T-C

Position:

• chr4-21331788-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.62-449079A>G		intron_variant		ENST00000382152.7	NP_079497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNIP4	ENST00000382152.7	c.62-449079A>G		intron_variant		5	NM_025221.6	ENSP00000371587
	ENST00000659675.1	n.212-13402T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.738

Alfa AF: 0.688 Hom.: 49943

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1364836; hg19: chr4-21333411;