4-20758466-T-G

Position:

• chr4-20758466-T-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.358+355A>C		intron_variant		ENST00000382152.7	NP_079497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNIP4	ENST00000382152.7	c.358+355A>C		intron_variant		5	NM_025221.6	ENSP00000371587

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

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.732

Alfa AF: 0.696 Hom.: 63297

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

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: rs4697177; hg19: chr4-20760089;