chr4-21237086-T-G

Variant names:

• chr4-21237086-T-G
• rs10516377
• NM_025221.6:c.62-354377A>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.62-354377A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0608 in 151,674 control chromosomes in the GnomAD database, including 327 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 0.061 (327 hom., cov: 32)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 1 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 (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.62-354377A>C		intron_variant	Intron 1 of 8	ENST00000382152.7	NP_079497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNIP4	ENST00000382152.7	c.62-354377A>C		intron_variant	Intron 1 of 8	5	NM_025221.6	ENSP00000371587.2

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 9208 AN: 151580 Hom.: 323 Cov.: 32

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0249

Gnomad FIN AF: 0.0488

Gnomad MID AF: 0.0609

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.0714

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

GnomAD4 genome AF: 0.0608 AC: 9226 AN: 151674 Hom.: 327 Cov.: 32 AF XY: 0.0607 AC XY: 4493 AN XY: 74076

African (AFR) AF: 0.0428 AC: 1772 AN: 41390

American (AMR) AF: 0.112 AC: 1708 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3470

East Asian (EAS) AF: 0.138 AC: 714 AN: 5172

South Asian (SAS) AF: 0.0254 AC: 122 AN: 4812

European-Finnish (FIN) AF: 0.0488 AC: 507 AN: 10386

Middle Eastern (MID) AF: 0.0625 AC: 18 AN: 288

European-Non Finnish (NFE) AF: 0.0596 AC: 4048 AN: 67940

Other (OTH) AF: 0.0703 AC: 148 AN: 2104

Alfa AF: 0.0580 Hom.: 59

Bravo AF: 0.0664

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.69
PhyloP100		-1.8
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: rs10516377; hg19: chr4-21238709;