15-90411783-G-A

Variant names:

• chr15-90411783-G-A
• rs2589949
• NM_003870.4:c.156-14327G>A

Variant summary

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

The NM_003870.4(IQGAP1):​c.156-14327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,994 control chromosomes in the GnomAD database, including 10,499 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 0.36 (10499 hom., cov: 31)
• Consequence: IQGAP1 NM_003870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 14 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 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.156-14327G>A		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.156-14327G>A		intron	N/A	ENSP00000268182.5
	IQGAP1	ENST00000560738.1	TSL:5	c.106+20959G>A		intron	N/A	ENSP00000453181.1
	IQGAP1	ENST00000560418.1	TSL:5	c.-309-14327G>A		intron	N/A	ENSP00000452723.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54693 AN: 151876 Hom.: 10468 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.360 AC: 54772 AN: 151994 Hom.: 10499 Cov.: 31 AF XY: 0.366 AC XY: 27191 AN XY: 74288

African (AFR) AF: 0.363 AC: 15015 AN: 41408

American (AMR) AF: 0.458 AC: 6996 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1042 AN: 3464

East Asian (EAS) AF: 0.666 AC: 3444 AN: 5172

South Asian (SAS) AF: 0.517 AC: 2490 AN: 4818

European-Finnish (FIN) AF: 0.327 AC: 3445 AN: 10548

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21214 AN: 67988

Other (OTH) AF: 0.362 AC: 764 AN: 2112

Alfa AF: 0.336 Hom.: 26349

Bravo AF: 0.373

Asia WGS AF: 0.561 AC: 1951 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.18
PhyloP100		0.28
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: rs2589949; hg19: chr15-90955015;