chr5-170644476-C-T

Position:

• chr5-170644476-C-T

Variant summary

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

The NM_014592.4(KCNIP1):​c.62-74282C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,090 control chromosomes in the GnomAD database, including 4,322 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 0.21 (4322 hom., cov: 33)
• Consequence: KCNIP1 NM_014592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236

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]

KCNIP1-AS1 (HGNC:40710): (KCNIP1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNIP1	NM_014592.4	c.62-74282C>T		intron_variant		ENST00000328939.9
KCNIP1-AS1	NR_136214.1	n.1125-2331G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNIP1	ENST00000328939.9	c.62-74282C>T		intron_variant		1	NM_014592.4	A1
KCNIP1-AS1	ENST00000523591.1	n.1092-2331G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31460 AN: 151972 Hom.: 4312 Cov.: 33

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.207 AC: 31502 AN: 152090 Hom.: 4322 Cov.: 33 AF XY: 0.206 AC XY: 15353 AN XY: 74352

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.168

Alfa AF: 0.125 Hom.: 1197

Bravo AF: 0.212

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.55

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: rs4867623; hg19: chr5-170071480;