NM_014592.4:c.62-50156C>T

Variant names:

• chr5-170668602-C-T
• rs11747249
• NM_014592.4:c.62-50156C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014592.4(KCNIP1):​c.62-50156C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 152,288 control chromosomes in the GnomAD database, including 457 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 0.068 (457 hom., cov: 33)
• Consequence: KCNIP1 NM_014592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP1	NM_014592.4	c.62-50156C>T		intron_variant	Intron 1 of 7	ENST00000328939.9	NP_055407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNIP1	ENST00000328939.9	c.62-50156C>T		intron_variant	Intron 1 of 7	1	NM_014592.4	ENSP00000329686.4

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10331 AN: 152170 Hom.: 457 Cov.: 33

Gnomad AFR AF: 0.0207

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.0863

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0923

Gnomad OTH AF: 0.0484

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

GnomAD4 genome AF: 0.0678 AC: 10320 AN: 152288 Hom.: 457 Cov.: 33 AF XY: 0.0695 AC XY: 5178 AN XY: 74458

African (AFR) AF: 0.0206 AC: 858 AN: 41576

American (AMR) AF: 0.0495 AC: 758 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3472

East Asian (EAS) AF: 0.0699 AC: 362 AN: 5180

South Asian (SAS) AF: 0.0853 AC: 412 AN: 4828

European-Finnish (FIN) AF: 0.133 AC: 1409 AN: 10598

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0923 AC: 6277 AN: 68020

Other (OTH) AF: 0.0474 AC: 100 AN: 2108

Alfa AF: 0.0726 Hom.: 925

Bravo AF: 0.0592

Asia WGS AF: 0.0590 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.57
PhyloP100		-1.8
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: rs11747249; hg19: chr5-170095606;