rs1019997

Variant names:

• chr4-20959056-G-T
• rs1019997
• NM_025221.6:c.62-76347C>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.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
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025221.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP4	NM_025221.6	MANE Select	c.62-76347C>A		intron	N/A	NP_079497.2
	KCNIP4	NM_001363504.2		c.112+24758C>A		intron	N/A	NP_001350433.1
	KCNIP4	NM_147183.3		c.101-108389C>A		intron	N/A	NP_671712.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP4	ENST00000382152.7	TSL:5 MANE Select	c.62-76347C>A		intron	N/A	ENSP00000371587.2
	KCNIP4	ENST00000382149.9	TSL:1	c.112+24758C>A		intron	N/A	ENSP00000494651.1
	KCNIP4	ENST00000382150.8	TSL:1	c.101-108389C>A		intron	N/A	ENSP00000371585.4

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

African (AFR) AF: 0.650 AC: 26944 AN: 41468

American (AMR) AF: 0.644 AC: 9841 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2351 AN: 3470

East Asian (EAS) AF: 0.742 AC: 3828 AN: 5160

South Asian (SAS) AF: 0.624 AC: 3006 AN: 4820

European-Finnish (FIN) AF: 0.529 AC: 5578 AN: 10554

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.557 AC: 37886 AN: 67980

Other (OTH) AF: 0.627 AC: 1326 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.68
PhyloP100		-1.4
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: rs1019997; hg19: chr4-20960679;