chr4-21194854-A-G

Position:

• chr4-21194854-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025221.6(KCNIP4):​c.62-312145T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,056 control chromosomes in the GnomAD database, including 17,272 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 0.44 (17272 hom., cov: 32)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNIP4	NM_025221.6	c.62-312145T>C		intron_variant		ENST00000382152.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNIP4	ENST00000382152.7	c.62-312145T>C		intron_variant		5	NM_025221.6

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67409 AN: 151938 Hom.: 17253 Cov.: 32

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.444 AC: 67473 AN: 152056 Hom.: 17272 Cov.: 32 AF XY: 0.443 AC XY: 32960 AN XY: 74324

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.421

Alfa AF: 0.368 Hom.: 6101

Bravo AF: 0.452

Asia WGS AF: 0.413 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.23
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6448032; hg19: chr4-21196477;