rs1858973

Positions:

• chr16-19732327-T-C

Variant summary

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

The NM_153208.3(IQCK):​c.247-1371T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,180 control chromosomes in the GnomAD database, including 2,165 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 0.16 (2165 hom., cov: 33)
• Consequence: IQCK NM_153208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

Genes affected

IQCK (HGNC:28556): (IQ motif containing K) This gene belongs to the IQ motif-containing family of proteins. The IQ motif serves as a binding site for different EF-hand proteins such as calmodulin. This gene was identified as a potential candidate gene for obsessive-compulsive disorder in a genome-wide association study. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCK	NM_153208.3	c.247-1371T>C		intron_variant		ENST00000695302.1	NP_694940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQCK	ENST00000695302.1	c.247-1371T>C		intron_variant			NM_153208.3	ENSP00000511791	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24698 AN: 152062 Hom.: 2156 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.163 AC: 24731 AN: 152180 Hom.: 2165 Cov.: 33 AF XY: 0.163 AC XY: 12146 AN XY: 74398

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.177

Alfa AF: 0.171 Hom.: 1608

Bravo AF: 0.158

Asia WGS AF: 0.277 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.74

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: rs1858973; hg19: chr16-19743649;