rs6817687

Variant names:

• chr4-21083707-T-C
• rs6817687
• NM_025221.6:c.62-200998A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025221.6(KCNIP4):​c.62-200998A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,894 control chromosomes in the GnomAD database, including 3,826 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 0.21 (3826 hom., cov: 31)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 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.62-200998A>G		intron	N/A	NP_079497.2
	KCNIP4	NM_147183.3		c.100+220100A>G		intron	N/A	NP_671712.1
	KCNIP4	NM_001035003.2		c.89-233040A>G		intron	N/A	NP_001030175.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP4	ENST00000382152.7	TSL:5 MANE Select	c.62-200998A>G		intron	N/A	ENSP00000371587.2
	KCNIP4	ENST00000382150.8	TSL:1	c.100+220100A>G		intron	N/A	ENSP00000371585.4
	KCNIP4	ENST00000382148.7	TSL:1	c.89-233040A>G		intron	N/A	ENSP00000371583.3

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32487 AN: 151776 Hom.: 3826 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.214 AC: 32509 AN: 151894 Hom.: 3826 Cov.: 31 AF XY: 0.215 AC XY: 15936 AN XY: 74250

African (AFR) AF: 0.261 AC: 10759 AN: 41292

American (AMR) AF: 0.185 AC: 2823 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 636 AN: 3464

East Asian (EAS) AF: 0.240 AC: 1234 AN: 5150

South Asian (SAS) AF: 0.169 AC: 817 AN: 4826

European-Finnish (FIN) AF: 0.220 AC: 2337 AN: 10606

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13308 AN: 67990

Other (OTH) AF: 0.218 AC: 460 AN: 2114

Alfa AF: 0.203 Hom.: 8474

Bravo AF: 0.214

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
DANN	Benign	0.50
PhyloP100		-1.7
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: rs6817687; hg19: chr4-21085330;