5-170416626-C-A

Variant names:

• chr5-170416626-C-A
• rs13175143
• ENST00000377360.8:c.88+62662C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000377360.8(KCNIP1):​c.88+62662C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 151,788 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 32)
• Consequence: KCNIP1 ENST00000377360.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784
• Publications: 4 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-OT1 (HGNC:40320): (KCNIP1 overlapping transcript 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP1	NM_001034838.3	c.88+62662C>A		intron_variant	Intron 1 of 7		NP_001030010.1
KCNIP1-OT1	NR_109899.1	n.112-3760C>A		intron_variant	Intron 1 of 2
KCNIP1	XM_017009407.2	c.88+62662C>A		intron_variant	Intron 2 of 8		XP_016864896.1
KCNIP1	XM_017009408.2	c.89-19160C>A		intron_variant	Intron 1 of 3		XP_016864897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNIP1	ENST00000377360.8	c.88+62662C>A		intron_variant	Intron 1 of 7	1		ENSP00000366577.4
KCNIP1-OT1	ENST00000518387.2	n.115-3760C>A		intron_variant	Intron 1 of 2	1
KCNIP1	ENST00000517344.1	n.88+62662C>A		intron_variant	Intron 1 of 3	3		ENSP00000431053.1
KCNIP1	ENST00000518527.1	n.478+62662C>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151788 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151788 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74084

African (AFR) AF: 0.00 AC: 0 AN: 41274

American (AMR) AF: 0.000197 AC: 3 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 3777

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.58
PhyloP100		0.78

Splicing

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

Other links and lift over

dbSNP: rs13175143; hg19: chr5-169843630;