rs876477

chr4-21155305-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.62-272596G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 152,064 control chromosomes in the GnomAD database, including 275 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 0.054 (275 hom., cov: 33)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNIP4	NM_025221.6	c.62-272596G>A		intron_variant		ENST00000382152.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNIP4	ENST00000382152.7	c.62-272596G>A		intron_variant		5	NM_025221.6

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8118 AN: 151946 Hom.: 271 Cov.: 33

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0895

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0536

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0535

Gnomad OTH AF: 0.0567

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

GnomAD4 genome AF: 0.0535 AC: 8137 AN: 152064 Hom.: 275 Cov.: 33 AF XY: 0.0543 AC XY: 4034 AN XY: 74312

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.0899

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.0289

Gnomad4 FIN AF: 0.0536

Gnomad4 NFE AF: 0.0535

Gnomad4 OTH AF: 0.0556

Alfa AF: 0.0503 Hom.: 29

Bravo AF: 0.0571

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.078
Dann	Benign	0.57

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: rs876477; hg19: chr4-21156928;