5-170416626-C-T

Variant summary

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

The ENST00000377360.8(KCNIP1):c.88+62662C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,844 control chromosomes in the GnomAD database, including 3,582 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 (3582 hom., cov: 32)
• Consequence: KCNIP1 ENST00000377360.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784

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-OT1 (HGNC:40320): (KCNIP1 overlapping transcript 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 (AMR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNIP1-OT1	NR_109899.1	n.112-3760C>T		intron_variant, non_coding_transcript_variant
KCNIP1	NM_001034838.3	c.88+62662C>T		intron_variant
KCNIP1	XM_017009407.2	c.88+62662C>T		intron_variant
KCNIP1	XM_017009408.2	c.89-19160C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNIP1	ENST00000377360.8	c.88+62662C>T		intron_variant		1		P4
KCNIP1-OT1	ENST00000518387.1	n.112-3760C>T		intron_variant, non_coding_transcript_variant		1
KCNIP1	ENST00000517344.1	c.88+62662C>T		intron_variant, NMD_transcript_variant		3
KCNIP1	ENST00000518527.1	n.478+62662C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32553 AN: 151728 Hom.: 3578 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.214 AC: 32570 AN: 151844 Hom.: 3582 Cov.: 32 AF XY: 0.218 AC XY: 16156 AN XY: 74180

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.197

Alfa AF: 0.189 Hom.: 2415

Bravo AF: 0.214

Asia WGS AF: 0.248 AC: 866 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	2.1
Dann	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13175143; hg19: chr5-169843630; COSMIC: COSV66173571;