rs7574862

Positions:

• chr2-95302457-A-G
• chr2-95302457-A-T

Variant summary

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

The NM_013434.5(KCNIP3):​c.15+5004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,224 control chromosomes in the GnomAD database, including 45,627 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 0.77 (45627 hom., cov: 33)
• Consequence: KCNIP3 NM_013434.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

Genes affected

KCNIP3 (HGNC:15523): (potassium voltage-gated channel interacting protein 3) This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins, which belong to the recoverin branch of the EF-hand superfamily. Members of this family are small calcium binding proteins containing EF-hand-like domains. They are integral subunit components of native Kv4 channel complexes that may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. The encoded protein also functions as a calcium-regulated transcriptional repressor, and interacts with presenilins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

KCNIP3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNIP3	NM_013434.5	c.15+5004A>G		intron_variant		ENST00000295225.10	NP_038462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNIP3	ENST00000295225.10	c.15+5004A>G		intron_variant		1	NM_013434.5	ENSP00000295225.5
KCNIP3	ENST00000475491.1	n.116+5004A>G		intron_variant		1
KCNIP3	ENST00000377181.2	n.107+5004A>G		intron_variant		5
KCNIP3	ENST00000461336.5	n.108-587A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117119 AN: 152106 Hom.: 45606 Cov.: 33

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.770 AC: 117182 AN: 152224 Hom.: 45627 Cov.: 33 AF XY: 0.768 AC XY: 57139 AN XY: 74422

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.788

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.778

Alfa AF: 0.765 Hom.: 8214

Bravo AF: 0.765

Asia WGS AF: 0.687 AC: 2393 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs7574862; hg19: chr2-95968205;