4-21662372-T-C

Position:

• chr4-21662372-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.61+286199A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,138 control chromosomes in the GnomAD database, including 26,351 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 0.58 (26351 hom., cov: 33)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.61+286199A>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.61+286199A>G		intron_variant		5	NM_025221.6	ENSP00000371587
KCNIP4	ENST00000382148.7	c.88+34978A>G		intron_variant		1		ENSP00000371583	A1
KCNIP4	ENST00000447367.6	c.61+286199A>G		intron_variant		5		ENSP00000399080
KCNIP4	ENST00000515786.2	c.*68+100549A>G		intron_variant, NMD_transcript_variant		5		ENSP00000445321

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88134 AN: 152020 Hom.: 26320 Cov.: 33

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.580 AC: 88217 AN: 152138 Hom.: 26351 Cov.: 33 AF XY: 0.588 AC XY: 43686 AN XY: 74356

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.577

Alfa AF: 0.527 Hom.: 28908

Bravo AF: 0.591

Asia WGS AF: 0.786 AC: 2733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4697227; hg19: chr4-21663995;