16-19755807-T-G

Position:

• chr16-19755807-T-G

Variant summary

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

The NM_153208.3(IQCK):​c.475-8041T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,184 control chromosomes in the GnomAD database, including 17,568 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 0.39 (17568 hom., cov: 32)
• Consequence: IQCK NM_153208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCK	NM_153208.3	c.475-8041T>G		intron_variant		ENST00000695302.1	NP_694940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQCK	ENST00000695302.1	c.475-8041T>G		intron_variant			NM_153208.3	ENSP00000511791	P1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59472 AN: 152066 Hom.: 17507 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.392 AC: 59592 AN: 152184 Hom.: 17568 Cov.: 32 AF XY: 0.385 AC XY: 28648 AN XY: 74412

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.366

Alfa AF: 0.234 Hom.: 10387

Bravo AF: 0.417

Asia WGS AF: 0.355 AC: 1236 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	4.4
DANN	Benign	0.70

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: rs8053136; hg19: chr16-19767129;