chr4-21221048-G-A

Variant names:

• chr4-21221048-G-A
• rs10516376
• NM_025221.6:c.62-338339C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025221.6(KCNIP4):​c.62-338339C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 152,158 control chromosomes in the GnomAD database, including 331 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 0.061 (331 hom., cov: 32)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.62-338339C>T		intron_variant	Intron 1 of 8	ENST00000382152.7	NP_079497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNIP4	ENST00000382152.7	c.62-338339C>T		intron_variant	Intron 1 of 8	5	NM_025221.6	ENSP00000371587.2

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9198 AN: 152040 Hom.: 327 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.0483

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0594

Gnomad OTH AF: 0.0700

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

GnomAD4 genome AF: 0.0606 AC: 9217 AN: 152158 Hom.: 331 Cov.: 32 AF XY: 0.0605 AC XY: 4498 AN XY: 74356

African (AFR) AF: 0.0433 AC: 1799 AN: 41528

American (AMR) AF: 0.112 AC: 1706 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3472

East Asian (EAS) AF: 0.133 AC: 685 AN: 5154

South Asian (SAS) AF: 0.0261 AC: 126 AN: 4830

European-Finnish (FIN) AF: 0.0483 AC: 511 AN: 10588

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0594 AC: 4038 AN: 67992

Other (OTH) AF: 0.0688 AC: 145 AN: 2108

Alfa AF: 0.0594 Hom.: 1206

Bravo AF: 0.0664

Asia WGS AF: 0.0680 AC: 238 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	3.6
DANN	Benign	0.75
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10516376; hg19: chr4-21222671;