chr4-21662372-T-C

Variant names:

• chr4-21662372-T-C
• rs4697227
• NM_025221.6:c.61+286199A>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.61+286199A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,138 control chromosomes in the GnomAD database, including 26,351 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 0.58 (26351 hom., cov: 33)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• 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 = 0.943 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+286199A>G		intron	N/A	NP_079497.2
	KCNIP4	NM_001035003.2		c.88+34978A>G		intron	N/A	NP_001030175.1	Q6PIL6-5
	KCNIP4	NM_147181.4		c.61+286199A>G		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+286199A>G		intron	N/A	ENSP00000371587.2	Q6PIL6-1
	KCNIP4	ENST00000382148.7	TSL:1	c.88+34978A>G		intron	N/A	ENSP00000371583.3	Q6PIL6-5
	KCNIP4	ENST00000447367.6	TSL:5	c.61+286199A>G		intron	N/A	ENSP00000399080.2	Q6PIL6-2

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88134 AN: 152020 Hom.: 26320 Cov.: 33

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.580 AC: 88217 AN: 152138 Hom.: 26351 Cov.: 33 AF XY: 0.588 AC XY: 43686 AN XY: 74356

African (AFR) AF: 0.617 AC: 25581 AN: 41490

American (AMR) AF: 0.675 AC: 10331 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3470

East Asian (EAS) AF: 0.965 AC: 4993 AN: 5172

South Asian (SAS) AF: 0.637 AC: 3076 AN: 4830

European-Finnish (FIN) AF: 0.565 AC: 5980 AN: 10580

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34414 AN: 67980

Other (OTH) AF: 0.577 AC: 1220 AN: 2114

Alfa AF: 0.532 Hom.: 37278

Bravo AF: 0.591

Asia WGS AF: 0.786 AC: 2733 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	1.2
DANN	Benign	0.60
PhyloP100		-2.0
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: rs4697227; hg19: chr4-21663995;