rs16871289

Variant names:

• chr4-21509760-C-T
• rs16871289
• NM_025221.6:c.61+438811G>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.61+438811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 152,106 control chromosomes in the GnomAD database, including 1,211 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 0.072 (1211 hom., cov: 31)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP4	NM_025221.6	MANE Select	c.61+438811G>A		intron	N/A	NP_079497.2
	KCNIP4	NM_001035003.2		c.88+187590G>A		intron	N/A	NP_001030175.1	Q6PIL6-5
	KCNIP4	NM_147181.4		c.61+438811G>A		intron	N/A	NP_671710.1	Q6PIL6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP4	ENST00000382152.7	TSL:5 MANE Select	c.61+438811G>A		intron	N/A	ENSP00000371587.2	Q6PIL6-1
	KCNIP4	ENST00000382148.7	TSL:1	c.88+187590G>A		intron	N/A	ENSP00000371583.3	Q6PIL6-5
	KCNIP4	ENST00000509207.1	TSL:1	c.-24+34630G>A		intron	N/A	ENSP00000423257.1	Q6PIL6-3

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10881 AN: 151988 Hom.: 1209 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.0550

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

GnomAD4 genome AF: 0.0717 AC: 10907 AN: 152106 Hom.: 1211 Cov.: 31 AF XY: 0.0694 AC XY: 5163 AN XY: 74368

African (AFR) AF: 0.242 AC: 10028 AN: 41436

American (AMR) AF: 0.0272 AC: 415 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0419 AC: 202 AN: 4820

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10602

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00131 AC: 89 AN: 68000

Other (OTH) AF: 0.0610 AC: 129 AN: 2114

Alfa AF: 0.0272 Hom.: 1224

Bravo AF: 0.0809

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.37
DANN	Benign	0.70
PhyloP100		-1.4
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: rs16871289; hg19: chr4-21511383;