15-90408284-T-C

Variant names:

• chr15-90408284-T-C
• rs10520688
• NM_003870.4:c.155+17411T>C

Variant summary

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

The NM_003870.4(IQGAP1):​c.155+17411T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,090 control chromosomes in the GnomAD database, including 2,199 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 (2199 hom., cov: 32)
• Consequence: IQGAP1 NM_003870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727
• Publications: 6 publications found

Genes affected

IQGAP1 (HGNC:6110): (IQ motif containing GTPase activating protein 1) This gene encodes a member of the IQGAP family. The protein contains four IQ domains, one calponin homology domain, one Ras-GAP domain and one WW domain. It interacts with components of the cytoskeleton, with cell adhesion molecules, and with several signaling molecules to regulate cell morphology and motility. Expression of the protein is upregulated by gene amplification in two gastric cancer cell lines. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQGAP1	NM_003870.4	c.155+17411T>C		intron_variant	Intron 2 of 37	ENST00000268182.10	NP_003861.1
IQGAP1	XM_047433204.1	c.155+17411T>C		intron_variant	Intron 2 of 29		XP_047289160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQGAP1	ENST00000268182.10	c.155+17411T>C		intron_variant	Intron 2 of 37	1	NM_003870.4	ENSP00000268182.5
IQGAP1	ENST00000560738.1	c.106+17460T>C		intron_variant	Intron 2 of 24	5		ENSP00000453181.1
IQGAP1	ENST00000560418.1	c.-309-17826T>C		intron_variant	Intron 1 of 6	5		ENSP00000452723.1
IQGAP1	ENST00000633485.1	n.155+17411T>C		intron_variant	Intron 2 of 38	5		ENSP00000488618.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23993 AN: 151972 Hom.: 2198 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.0870

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.158 AC: 24003 AN: 152090 Hom.: 2199 Cov.: 32 AF XY: 0.152 AC XY: 11338 AN XY: 74374

African (AFR) AF: 0.246 AC: 10192 AN: 41458

American (AMR) AF: 0.147 AC: 2240 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3468

East Asian (EAS) AF: 0.0505 AC: 261 AN: 5172

South Asian (SAS) AF: 0.0490 AC: 236 AN: 4816

European-Finnish (FIN) AF: 0.0870 AC: 923 AN: 10606

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9232 AN: 67986

Other (OTH) AF: 0.150 AC: 317 AN: 2112

Alfa AF: 0.130 Hom.: 1464

Bravo AF: 0.170

Asia WGS AF: 0.0610 AC: 212 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.52
PhyloP100		-0.73
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: rs10520688; hg19: chr15-90951516;