rs358592

Positions:

• chr4-21475367-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025221.6(KCNIP4):​c.61+473204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,918 control chromosomes in the GnomAD database, including 36,575 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 0.69 (36575 hom., cov: 31)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNIP4	NM_025221.6	c.61+473204G>A		intron_variant		ENST00000382152.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNIP4	ENST00000382152.7	c.61+473204G>A		intron_variant		5	NM_025221.6

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104761 AN: 151800 Hom.: 36528 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.690 AC: 104859 AN: 151918 Hom.: 36575 Cov.: 31 AF XY: 0.682 AC XY: 50608 AN XY: 74220

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.656

Alfa AF: 0.672 Hom.: 75599

Bravo AF: 0.696

Asia WGS AF: 0.684 AC: 2378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.16
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs358592; hg19: chr4-21476990;