rs1019997

chr4-20959056-G-T

Variant summary

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

The NM_025221.6(KCNIP4):c.62-76347C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,050 control chromosomes in the GnomAD database, including 27,858 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 0.60 (27858 hom., cov: 33)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNIP4	NM_025221.6	c.62-76347C>A		intron_variant		ENST00000382152.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNIP4	ENST00000382152.7	c.62-76347C>A		intron_variant		5	NM_025221.6

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91514 AN: 151930 Hom.: 27828 Cov.: 33

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.602 AC: 91594 AN: 152050 Hom.: 27858 Cov.: 33 AF XY: 0.606 AC XY: 45018 AN XY: 74308

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.627

Alfa AF: 0.592 Hom.: 4261

Bravo AF: 0.618

Asia WGS AF: 0.655 AC: 2279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.65
Dann	Benign	0.68

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: rs1019997; hg19: chr4-20960679;