15-90431158-G-C

Variant names:

• chr15-90431158-G-C
• rs8035980
• NM_003870.4:c.390+1492G>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.390+1492G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,076 control chromosomes in the GnomAD database, including 25,445 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 0.56 (25445 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: IQGAP1 NM_003870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003870.4. 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
	IQGAP1	NM_003870.4	MANE Select	c.390+1492G>C		intron	N/A	NP_003861.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQGAP1	ENST00000268182.10	TSL:1 MANE Select	c.390+1492G>C		intron	N/A	ENSP00000268182.5
	IQGAP1	ENST00000921154.1		c.390+1492G>C		intron	N/A	ENSP00000591213.1
	IQGAP1	ENST00000921153.1		c.390+1492G>C		intron	N/A	ENSP00000591212.1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 84691 AN: 150988 Hom.: 25410 Cov.: 31

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.561 AC: 84771 AN: 151076 Hom.: 25445 Cov.: 31 AF XY: 0.562 AC XY: 41477 AN XY: 73746

African (AFR) AF: 0.750 AC: 30954 AN: 41290

American (AMR) AF: 0.605 AC: 9146 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1409 AN: 3458

East Asian (EAS) AF: 0.828 AC: 4280 AN: 5168

South Asian (SAS) AF: 0.602 AC: 2900 AN: 4814

European-Finnish (FIN) AF: 0.429 AC: 4387 AN: 10226

Middle Eastern (MID) AF: 0.497 AC: 142 AN: 286

European-Non Finnish (NFE) AF: 0.442 AC: 29960 AN: 67720

Other (OTH) AF: 0.540 AC: 1129 AN: 2092

Alfa AF: 0.334 Hom.: 810

Bravo AF: 0.588

Asia WGS AF: 0.695 AC: 2417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.38
PhyloP100		-1.6
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: rs8035980; hg19: chr15-90974390;