NM_173191.3:c.74-3972A>G

Variant names:

• chr10-101835139-T-C
• rs755381
• NM_173191.3:c.74-3972A>G

Variant summary

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

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]

ENSG00000308219 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNIP2	NM_173191.3	c.74-3972A>G		intron_variant	Intron 1 of 9	ENST00000356640.7	NP_775283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNIP2	ENST00000356640.7	c.74-3972A>G		intron_variant	Intron 1 of 9	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

African (AFR) AF: 0.191 AC: 7924 AN: 41444

American (AMR) AF: 0.209 AC: 3187 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 923 AN: 3470

East Asian (EAS) AF: 0.484 AC: 2497 AN: 5156

South Asian (SAS) AF: 0.277 AC: 1335 AN: 4822

European-Finnish (FIN) AF: 0.121 AC: 1277 AN: 10594

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12319 AN: 67982

Other (OTH) AF: 0.209 AC: 442 AN: 2114

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
PhyloP100		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
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: rs755381; hg19: chr10-103594896;