4-21816098-C-T

Variant names:

• chr4-21816098-C-T
• rs4282162
• NM_025221.6:c.61+132473G>A

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+132473G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,870 control chromosomes in the GnomAD database, including 12,648 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 0.38 (12648 hom., cov: 31)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.61+132473G>A		intron_variant	Intron 1 of 8	ENST00000382152.7	NP_079497.2
KCNIP4	NM_147181.4	c.61+132473G>A		intron_variant	Intron 1 of 7		NP_671710.1
KCNIP4	NM_147182.4	c.-135-53066G>A		intron_variant	Intron 1 of 8		NP_671711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNIP4	ENST00000382152.7	c.61+132473G>A		intron_variant	Intron 1 of 8	5	NM_025221.6	ENSP00000371587.2
KCNIP4	ENST00000447367.6	c.61+132473G>A		intron_variant	Intron 1 of 7	5		ENSP00000399080.2
KCNIP4	ENST00000512102.1	n.46+39572G>A		intron_variant	Intron 1 of 2	5
KCNIP4	ENST00000515786.2	n.62-53066G>A		intron_variant	Intron 1 of 8	5		ENSP00000445321.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58039 AN: 151752 Hom.: 12649 Cov.: 31

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.382 AC: 58046 AN: 151870 Hom.: 12648 Cov.: 31 AF XY: 0.378 AC XY: 28048 AN XY: 74218

African (AFR) AF: 0.194 AC: 8027 AN: 41434

American (AMR) AF: 0.301 AC: 4591 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1384 AN: 3462

East Asian (EAS) AF: 0.248 AC: 1276 AN: 5154

South Asian (SAS) AF: 0.337 AC: 1618 AN: 4798

European-Finnish (FIN) AF: 0.491 AC: 5184 AN: 10550

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34669 AN: 67894

Other (OTH) AF: 0.386 AC: 814 AN: 2110

Alfa AF: 0.463 Hom.: 8868

Bravo AF: 0.353

Asia WGS AF: 0.338 AC: 1175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.56
PhyloP100		0.10
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: rs4282162; hg19: chr4-21817721;