rs1604805

Positions:

• chr4-21569464-T-C

Variant summary

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

The NM_025221.6(KCNIP4):​c.61+379107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 151,966 control chromosomes in the GnomAD database, including 316 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 0.057 (316 hom., cov: 31)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNIP4	NM_025221.6	c.61+379107A>G		intron_variant		ENST00000382152.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNIP4	ENST00000382152.7	c.61+379107A>G		intron_variant		5	NM_025221.6
KCNIP4	ENST00000382148.7	c.88+127886A>G		intron_variant		1		A1
KCNIP4	ENST00000447367.6	c.61+379107A>G		intron_variant		5
KCNIP4	ENST00000515786.2	c.*68+193457A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8657 AN: 151848 Hom.: 315 Cov.: 31

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.0791

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0435

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.0776

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.0765

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

GnomAD4 genome AF: 0.0570 AC: 8657 AN: 151966 Hom.: 316 Cov.: 31 AF XY: 0.0589 AC XY: 4376 AN XY: 74278

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.0789

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0440

Gnomad4 SAS AF: 0.0786

Gnomad4 FIN AF: 0.0776

Gnomad4 NFE AF: 0.0670

Gnomad4 OTH AF: 0.0752

Alfa AF: 0.0723 Hom.: 633

Bravo AF: 0.0560

Asia WGS AF: 0.0450 AC: 158 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.80
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1604805; hg19: chr4-21571087;