rs6448033

Positions:

• chr4-21198401-G-A

Variant summary

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

The NM_025221.6(KCNIP4):​c.62-315692C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,060 control chromosomes in the GnomAD database, including 16,983 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 (16983 hom., cov: 32)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.62-315692C>T		intron_variant		ENST00000382152.7	NP_079497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNIP4	ENST00000382152.7	c.62-315692C>T		intron_variant		5	NM_025221.6	ENSP00000371587

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66899 AN: 151942 Hom.: 16961 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.440 AC: 66967 AN: 152060 Hom.: 16983 Cov.: 32 AF XY: 0.440 AC XY: 32728 AN XY: 74348

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.323

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: 0.417

Alfa AF: 0.351 Hom.: 12197

Bravo AF: 0.447

Asia WGS AF: 0.411 AC: 1429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.52
DANN	Benign	0.66

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: rs6448033; hg19: chr4-21200024;