4-20886813-G-T

Variant names:

• chr4-20886813-G-T
• rs1156304
• NM_025221.6:c.62-4104C>A

Variant summary

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

The NM_025221.6(KCNIP4):​c.62-4104C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,030 control chromosomes in the GnomAD database, including 30,604 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 0.63 (30604 hom., cov: 33)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.62-4104C>A		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.62-4104C>A		intron_variant	Intron 1 of 8	5	NM_025221.6	ENSP00000371587.2

Frequencies

GnomAD3 genomes AF: 0.625 AC: 95013 AN: 151912 Hom.: 30555 Cov.: 33

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.626 AC: 95112 AN: 152030 Hom.: 30604 Cov.: 33 AF XY: 0.623 AC XY: 46326 AN XY: 74304

African (AFR) AF: 0.779 AC: 32326 AN: 41502

American (AMR) AF: 0.636 AC: 9709 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1982 AN: 3468

East Asian (EAS) AF: 0.598 AC: 3081 AN: 5152

South Asian (SAS) AF: 0.590 AC: 2838 AN: 4814

European-Finnish (FIN) AF: 0.500 AC: 5286 AN: 10566

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.555 AC: 37688 AN: 67952

Other (OTH) AF: 0.641 AC: 1354 AN: 2112

Alfa AF: 0.565 Hom.: 27281

Bravo AF: 0.647

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.49
PhyloP100		-0.41
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: rs1156304; hg19: chr4-20888436;