NM_025221.6:c.358+355A>C

Variant names:

• chr4-20758466-T-G
• rs4697177
• NM_025221.6:c.358+355A>C

Variant summary

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

The NM_025221.6(KCNIP4):​c.358+355A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 151,956 control chromosomes in the GnomAD database, including 40,027 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 0.72 (40027 hom., cov: 31)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• Publications: 7 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]

PACRGL (HGNC:28442): (parkin coregulated like)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.358+355A>C		intron_variant	Intron 4 of 8	ENST00000382152.7	NP_079497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNIP4	ENST00000382152.7	c.358+355A>C		intron_variant	Intron 4 of 8	5	NM_025221.6	ENSP00000371587.2

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109932 AN: 151838 Hom.: 40000 Cov.: 31

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.724 AC: 110009 AN: 151956 Hom.: 40027 Cov.: 31 AF XY: 0.723 AC XY: 53721 AN XY: 74252

African (AFR) AF: 0.796 AC: 32997 AN: 41454

American (AMR) AF: 0.737 AC: 11243 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2460 AN: 3470

East Asian (EAS) AF: 0.629 AC: 3228 AN: 5130

South Asian (SAS) AF: 0.700 AC: 3373 AN: 4820

European-Finnish (FIN) AF: 0.674 AC: 7116 AN: 10560

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47167 AN: 67954

Other (OTH) AF: 0.732 AC: 1547 AN: 2112

Alfa AF: 0.698 Hom.: 75306

Bravo AF: 0.729

Asia WGS AF: 0.682 AC: 2370 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.3
DANN	Benign	0.47
PhyloP100		0.44
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: rs4697177; hg19: chr4-20760089;