chr2-95302457-A-G

Variant names:

• chr2-95302457-A-G
• rs7574862
• NM_013434.5:c.15+5004A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

PROM2 (HGNC:20685): (prominin 2) This gene encodes a member of the prominin family of pentaspan membrane glycoproteins. The encoded protein localizes to basal epithelial cells and may be involved in the organization of plasma membrane microdomains. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013434.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP3	NM_013434.5	MANE Select	c.15+5004A>G		intron	N/A	NP_038462.1	Q9Y2W7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP3	ENST00000295225.10	TSL:1 MANE Select	c.15+5004A>G		intron	N/A	ENSP00000295225.5	Q9Y2W7-1
	KCNIP3	ENST00000475491.1	TSL:1	n.116+5004A>G		intron	N/A
	KCNIP3	ENST00000873168.1		c.15+5004A>G		intron	N/A	ENSP00000543227.1

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

African (AFR) AF: 0.872 AC: 36256 AN: 41562

American (AMR) AF: 0.683 AC: 10440 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2736 AN: 3472

East Asian (EAS) AF: 0.576 AC: 2972 AN: 5156

South Asian (SAS) AF: 0.674 AC: 3249 AN: 4820

European-Finnish (FIN) AF: 0.761 AC: 8063 AN: 10600

Middle Eastern (MID) AF: 0.723 AC: 211 AN: 292

European-Non Finnish (NFE) AF: 0.747 AC: 50823 AN: 68000

Other (OTH) AF: 0.778 AC: 1647 AN: 2116

Alfa AF: 0.767 Hom.: 8504

Bravo AF: 0.765

Asia WGS AF: 0.687 AC: 2393 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.78
PhyloP100		-0.28
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: rs7574862; hg19: chr2-95968205;