chr4-20881348-C-A

Variant names:

• chr4-20881348-C-A
• rs10516367
• NM_025221.6:c.163+1260G>T

Variant summary

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

The NM_025221.6(KCNIP4):​c.163+1260G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 151,974 control chromosomes in the GnomAD database, including 2,679 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 0.18 (2679 hom., cov: 32)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 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.163+1260G>T		intron	N/A	NP_079497.2
	KCNIP4	NM_001363504.2		c.113-30681G>T		intron	N/A	NP_001350433.1	Q3YAB7
	KCNIP4	NM_147183.3		c.101-30681G>T		intron	N/A	NP_671712.1	Q6PIL6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP4	ENST00000382152.7	TSL:5 MANE Select	c.163+1260G>T		intron	N/A	ENSP00000371587.2	Q6PIL6-1
	KCNIP4	ENST00000382149.9	TSL:1	c.113-30681G>T		intron	N/A	ENSP00000494651.1	Q3YAB7
	KCNIP4	ENST00000382150.8	TSL:1	c.101-30681G>T		intron	N/A	ENSP00000371585.4	Q6PIL6-4

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27240 AN: 151856 Hom.: 2675 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.179 AC: 27263 AN: 151974 Hom.: 2679 Cov.: 32 AF XY: 0.179 AC XY: 13333 AN XY: 74294

African (AFR) AF: 0.246 AC: 10193 AN: 41442

American (AMR) AF: 0.121 AC: 1849 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 806 AN: 3466

East Asian (EAS) AF: 0.205 AC: 1059 AN: 5162

South Asian (SAS) AF: 0.333 AC: 1600 AN: 4812

European-Finnish (FIN) AF: 0.112 AC: 1181 AN: 10564

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9952 AN: 67960

Other (OTH) AF: 0.169 AC: 357 AN: 2112

Alfa AF: 0.158 Hom.: 1723

Bravo AF: 0.179

Asia WGS AF: 0.220 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.3
DANN	Benign	0.80
PhyloP100		0.027
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: rs10516367; hg19: chr4-20882971;