rs719473

Variant names:

• chr15-90454832-A-G
• rs719473
• NM_003870.4:c.1612+280A>G

Variant summary

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

The NM_003870.4(IQGAP1):​c.1612+280A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,098 control chromosomes in the GnomAD database, including 2,801 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 0.19 (2801 hom., cov: 32)
• Consequence: IQGAP1 NM_003870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQGAP1	NM_003870.4	c.1612+280A>G		intron_variant	Intron 14 of 37	ENST00000268182.10	NP_003861.1
IQGAP1	XM_047433204.1	c.1612+280A>G		intron_variant	Intron 14 of 29		XP_047289160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQGAP1	ENST00000268182.10	c.1612+280A>G		intron_variant	Intron 14 of 37	1	NM_003870.4	ENSP00000268182.5
IQGAP1	ENST00000560738.1	c.107-11215A>G		intron_variant	Intron 2 of 24	5		ENSP00000453181.1
IQGAP1	ENST00000633485.1	n.1612+280A>G		intron_variant	Intron 14 of 38	5		ENSP00000488618.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28562 AN: 151980 Hom.: 2791 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.188 AC: 28593 AN: 152098 Hom.: 2801 Cov.: 32 AF XY: 0.187 AC XY: 13915 AN XY: 74346

African (AFR) AF: 0.207 AC: 8582 AN: 41480

American (AMR) AF: 0.125 AC: 1904 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3468

East Asian (EAS) AF: 0.212 AC: 1098 AN: 5174

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4820

European-Finnish (FIN) AF: 0.184 AC: 1951 AN: 10588

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12650 AN: 67982

Other (OTH) AF: 0.188 AC: 397 AN: 2112

Alfa AF: 0.189 Hom.: 1463

Bravo AF: 0.184

Asia WGS AF: 0.247 AC: 861 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	0.43
DANN	Benign	0.56
PhyloP100		-0.83
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: rs719473; hg19: chr15-90998064;