chr4-21509760-C-T

Position:

• chr4-21509760-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025221.6(KCNIP4):​c.61+438811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 152,106 control chromosomes in the GnomAD database, including 1,211 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 0.072 (1211 hom., cov: 31)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNIP4	NM_025221.6	c.61+438811G>A		intron_variant		ENST00000382152.7	NP_079497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNIP4	ENST00000382152.7	c.61+438811G>A		intron_variant		5	NM_025221.6	ENSP00000371587

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10881 AN: 151988 Hom.: 1209 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.0550

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

GnomAD4 genome AF: 0.0717 AC: 10907 AN: 152106 Hom.: 1211 Cov.: 31 AF XY: 0.0694 AC XY: 5163 AN XY: 74368

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.0272

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0419

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00131

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0117 Hom.: 315

Bravo AF: 0.0809

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.37
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16871289; hg19: chr4-21511383;