5-170715913-C-T

Variant names:

• chr5-170715913-C-T
• rs1541665
• NM_014592.4:c.62-2845C>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.62-2845C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,140 control chromosomes in the GnomAD database, including 5,125 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 0.22 (5125 hom., cov: 32)
• Consequence: KCNIP1 NM_014592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 9 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014592.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP1	NM_014592.4	MANE Select	c.62-2845C>T		intron	N/A	NP_055407.1
	KCNIP1	NM_001278339.2		c.62-2845C>T		intron	N/A	NP_001265268.1
	KCNIP1	NM_001034837.3		c.95-2845C>T		intron	N/A	NP_001030009.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP1	ENST00000328939.9	TSL:1 MANE Select	c.62-2845C>T		intron	N/A	ENSP00000329686.4
	KCNIP1	ENST00000434108.5	TSL:1	c.62-2845C>T		intron	N/A	ENSP00000414886.1
	KCNIP1	ENST00000411494.5	TSL:1	c.95-2845C>T		intron	N/A	ENSP00000395323.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33712 AN: 152022 Hom.: 5119 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.222 AC: 33745 AN: 152140 Hom.: 5125 Cov.: 32 AF XY: 0.232 AC XY: 17248 AN XY: 74394

African (AFR) AF: 0.225 AC: 9336 AN: 41504

American (AMR) AF: 0.344 AC: 5253 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3470

East Asian (EAS) AF: 0.808 AC: 4173 AN: 5162

South Asian (SAS) AF: 0.383 AC: 1847 AN: 4822

European-Finnish (FIN) AF: 0.157 AC: 1662 AN: 10592

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10367 AN: 67994

Other (OTH) AF: 0.200 AC: 420 AN: 2104

Alfa AF: 0.180 Hom.: 12331

Bravo AF: 0.237

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		-0.078
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: rs1541665; hg19: chr5-170142917;