rs16870989

Variant names:

• chr4-21385141-T-A
• rs16870989
• NM_025221.6:c.62-502432A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-21385141-T-A
• chr4-21385141-T-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.62-502432A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,142 control chromosomes in the GnomAD database, including 6,660 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 0.28 (6660 hom., cov: 33)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 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.62-502432A>T		intron	N/A	NP_079497.2
	KCNIP4	NM_001035003.2		c.88+312209A>T		intron	N/A	NP_001030175.1
	KCNIP4	NM_147181.4		c.62-534474A>T		intron	N/A	NP_671710.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP4	ENST00000382152.7	TSL:5 MANE Select	c.62-502432A>T		intron	N/A	ENSP00000371587.2
	KCNIP4	ENST00000382148.7	TSL:1	c.88+312209A>T		intron	N/A	ENSP00000371583.3
	KCNIP4	ENST00000509207.1	TSL:1	c.-24+159249A>T		intron	N/A	ENSP00000423257.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41953 AN: 152026 Hom.: 6655 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.276 AC: 41971 AN: 152142 Hom.: 6660 Cov.: 33 AF XY: 0.282 AC XY: 20951 AN XY: 74372

African (AFR) AF: 0.127 AC: 5277 AN: 41558

American (AMR) AF: 0.248 AC: 3787 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 890 AN: 3472

East Asian (EAS) AF: 0.412 AC: 2116 AN: 5138

South Asian (SAS) AF: 0.402 AC: 1937 AN: 4822

European-Finnish (FIN) AF: 0.427 AC: 4518 AN: 10578

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.331 AC: 22472 AN: 67976

Other (OTH) AF: 0.259 AC: 547 AN: 2110

Alfa AF: 0.305 Hom.: 936

Bravo AF: 0.252

Asia WGS AF: 0.371 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.48
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16870989; hg19: chr4-21386764;