10-101839568-A-T

Position:

• chr10-101839568-A-T

Variant summary

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

The NM_173191.3(KCNIP2):​c.73+3928T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,766 control chromosomes in the GnomAD database, including 22,677 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 0.54 (22677 hom., cov: 30)
• Consequence: KCNIP2 NM_173191.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850

Genes affected

KCNIP2 (HGNC:15522): (potassium voltage-gated channel interacting protein 2) This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belongs 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. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified from this gene. [provided by RefSeq, Jul 2008]

KCNIP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNIP2	NM_173191.3	c.73+3928T>A		intron_variant		ENST00000356640.7	NP_775283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNIP2	ENST00000356640.7	c.73+3928T>A		intron_variant		1	NM_173191.3	ENSP00000349055.2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82344 AN: 151648 Hom.: 22653 Cov.: 30

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.543 AC: 82415 AN: 151766 Hom.: 22677 Cov.: 30 AF XY: 0.544 AC XY: 40352 AN XY: 74168

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.570

Alfa AF: 0.561 Hom.: 2959

Bravo AF: 0.540

Asia WGS AF: 0.552 AC: 1921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.47

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: rs874885; hg19: chr10-103599325;