rs11957313

Positions:

• chr5-170523390-G-A
• chr5-170523390-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014592.4(KCNIP1):​c.61+18757G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,202 control chromosomes in the GnomAD database, including 3,085 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 0.19 (3085 hom., cov: 33)
• Consequence: KCNIP1 NM_014592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

Genes affected

KCNIP1 (HGNC:15521): (potassium voltage-gated channel interacting protein 1) This gene encodes a member of the family of cytosolic voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the neuronal calcium sensor (NCS) family of the calcium binding EF-hand proteins. They associate with Kv4 alpha subunits to form native Kv4 channel complexes. The encoded protein may regulate rapidly inactivating (A-type) currents, and hence neuronal membrane excitability, in response to changes in the concentration of intracellular calcium. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNIP1	NM_014592.4	c.61+18757G>A		intron_variant		ENST00000328939.9	NP_055407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNIP1	ENST00000328939.9	c.61+18757G>A		intron_variant		1	NM_014592.4	ENSP00000329686.4

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28469 AN: 152084 Hom.: 3076 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0977

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.187 AC: 28508 AN: 152202 Hom.: 3085 Cov.: 33 AF XY: 0.184 AC XY: 13689 AN XY: 74406

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0977

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.158

Alfa AF: 0.147 Hom.: 3158

Bravo AF: 0.194

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.82

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: rs11957313; hg19: chr5-169950394;