16-19755807-T-G

Variant names:

• chr16-19755807-T-G
• rs8053136
• NM_153208.3:c.475-8041T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

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 = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCK	NM_153208.3	MANE Select	c.475-8041T>G		intron	N/A	NP_694940.1
	IQCK	NM_001394804.1		c.475-8041T>G		intron	N/A	NP_001381733.1
	IQCK	NM_001394806.1		c.475-8041T>G		intron	N/A	NP_001381735.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCK	ENST00000695302.1	MANE Select	c.475-8041T>G		intron	N/A	ENSP00000511791.1
	IQCK	ENST00000320394.10	TSL:1	c.475-8041T>G		intron	N/A	ENSP00000324901.6
	IQCK	ENST00000308214.13	TSL:1	n.474+20357T>G		intron	N/A	ENSP00000309261.9

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

African (AFR) AF: 0.832 AC: 34569 AN: 41532

American (AMR) AF: 0.259 AC: 3960 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3462

East Asian (EAS) AF: 0.228 AC: 1181 AN: 5170

South Asian (SAS) AF: 0.334 AC: 1611 AN: 4826

European-Finnish (FIN) AF: 0.160 AC: 1702 AN: 10612

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14343 AN: 67976

Other (OTH) AF: 0.366 AC: 773 AN: 2110

Alfa AF: 0.268 Hom.: 22768

Bravo AF: 0.417

Asia WGS AF: 0.355 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.70
PhyloP100		-0.57
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: rs8053136; hg19: chr16-19767129;