rs11942476

Variant names:

• chr4-21453634-C-G
• rs11942476
• NM_025221.6:c.61+494937G>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.61+494937G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,128 control chromosomes in the GnomAD database, including 1,220 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 0.12 (1220 hom., cov: 32)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 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+494937G>C		intron	N/A	NP_079497.2
	KCNIP4	NM_001035003.2		c.88+243716G>C		intron	N/A	NP_001030175.1	Q6PIL6-5
	KCNIP4	NM_147181.4		c.61+494937G>C		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+494937G>C		intron	N/A	ENSP00000371587.2	Q6PIL6-1
	KCNIP4	ENST00000382148.7	TSL:1	c.88+243716G>C		intron	N/A	ENSP00000371583.3	Q6PIL6-5
	KCNIP4	ENST00000509207.1	TSL:1	c.-24+90756G>C		intron	N/A	ENSP00000423257.1	Q6PIL6-3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17705 AN: 152010 Hom.: 1217 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0901

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.116 AC: 17716 AN: 152128 Hom.: 1220 Cov.: 32 AF XY: 0.113 AC XY: 8431 AN XY: 74362

African (AFR) AF: 0.0732 AC: 3037 AN: 41490

American (AMR) AF: 0.0900 AC: 1376 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3470

East Asian (EAS) AF: 0.000776 AC: 4 AN: 5156

South Asian (SAS) AF: 0.153 AC: 738 AN: 4816

European-Finnish (FIN) AF: 0.117 AC: 1245 AN: 10610

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10548 AN: 67984

Other (OTH) AF: 0.120 AC: 254 AN: 2112

Alfa AF: 0.141 Hom.: 199

Bravo AF: 0.110

Asia WGS AF: 0.0680 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		-0.43
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: rs11942476; hg19: chr4-21455257;