10-101835139-T-C

Position:

• chr10-101835139-T-C

Variant summary

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

The NM_173191.3(KCNIP2):​c.74-3972A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,068 control chromosomes in the GnomAD database, including 3,286 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 0.20 (3286 hom., cov: 32)
• Consequence: KCNIP2 NM_173191.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNIP2	NM_173191.3	c.74-3972A>G		intron_variant		ENST00000356640.7	NP_775283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNIP2	ENST00000356640.7	c.74-3972A>G		intron_variant		1	NM_173191.3	ENSP00000349055.2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30073 AN: 151950 Hom.: 3279 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.198 AC: 30091 AN: 152068 Hom.: 3286 Cov.: 32 AF XY: 0.199 AC XY: 14829 AN XY: 74350

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.209

Alfa AF: 0.178 Hom.: 399

Bravo AF: 0.206

Asia WGS AF: 0.347 AC: 1206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.5
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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: rs755381; hg19: chr10-103594896;