4-20873323-C-T

Variant names:

• chr4-20873323-C-T
• rs1491371
• NM_025221.6:c.163+9285G>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.163+9285G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 152,304 control chromosomes in the GnomAD database, including 74,256 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 0.99 (74256 hom., cov: 33)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.163+9285G>A		intron_variant	Intron 2 of 8	ENST00000382152.7	NP_079497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNIP4	ENST00000382152.7	c.163+9285G>A		intron_variant	Intron 2 of 8	5	NM_025221.6	ENSP00000371587.2

Frequencies

GnomAD3 genomes AF: 0.987 AC: 150260 AN: 152186 Hom.: 74201 Cov.: 33

Gnomad AFR AF: 0.994

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 0.928

Gnomad SAS AF: 0.993

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.988

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

GnomAD4 genome AF: 0.987 AC: 150374 AN: 152304 Hom.: 74256 Cov.: 33 AF XY: 0.988 AC XY: 73547 AN XY: 74458

African (AFR) AF: 0.994 AC: 41324 AN: 41572

American (AMR) AF: 0.988 AC: 15103 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3461 AN: 3472

East Asian (EAS) AF: 0.927 AC: 4788 AN: 5164

South Asian (SAS) AF: 0.993 AC: 4795 AN: 4830

European-Finnish (FIN) AF: 0.993 AC: 10557 AN: 10630

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67082 AN: 68032

Other (OTH) AF: 0.988 AC: 2090 AN: 2116

Alfa AF: 0.986 Hom.: 18981

Bravo AF: 0.986

Asia WGS AF: 0.973 AC: 3384 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	0.40
DANN	Benign	0.50
PhyloP100		-0.34
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: rs1491371; hg19: chr4-20874946;