5-170668602-C-T

Position:

• chr5-170668602-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.62-50156C>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

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=-0.92).
• 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/exons	MANE	UniProt
KCNIP1	NM_014592.4	c.62-50156C>T		intron_variant		ENST00000328939.9
KCNIP1-AS1	NR_136214.1	n.1124+9805G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNIP1	ENST00000328939.9	c.62-50156C>T		intron_variant		1	NM_014592.4	A1
KCNIP1-AS1	ENST00000523591.1	n.1091+9805G>A		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.0206

Gnomad4 AMR AF: 0.0495

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.0699

Gnomad4 SAS AF: 0.0853

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.0923

Gnomad4 OTH AF: 0.0474

Alfa AF: 0.0778 Hom.: 705

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

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: rs11747249; hg19: chr5-170095606;