rs9968699

Variant names:

• chr5-170645494-A-G
• rs9968699
• NM_014592.4:c.62-73264A>G

Variant summary

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

The NM_014592.4(KCNIP1):​c.62-73264A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,208 control chromosomes in the GnomAD database, including 1,085 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 0.11 (1085 hom., cov: 33)
• Consequence: KCNIP1 NM_014592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNIP1	NM_014592.4	c.62-73264A>G		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.62-73264A>G		intron_variant	Intron 1 of 7	1	NM_014592.4	ENSP00000329686.4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16947 AN: 152090 Hom.: 1085 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0400

Gnomad EAS AF: 0.0902

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.111 AC: 16948 AN: 152208 Hom.: 1085 Cov.: 33 AF XY: 0.112 AC XY: 8348 AN XY: 74434

African (AFR) AF: 0.158 AC: 6550 AN: 41510

American (AMR) AF: 0.0669 AC: 1023 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 139 AN: 3472

East Asian (EAS) AF: 0.0895 AC: 463 AN: 5176

South Asian (SAS) AF: 0.0998 AC: 480 AN: 4812

European-Finnish (FIN) AF: 0.134 AC: 1421 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0978 AC: 6654 AN: 68012

Other (OTH) AF: 0.0885 AC: 187 AN: 2114

Alfa AF: 0.0942 Hom.: 1505

Bravo AF: 0.109

Asia WGS AF: 0.0970 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.71
PhyloP100		0.22
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: rs9968699; hg19: chr5-170072498;