rs2589949

Positions:

• chr15-90411783-G-A
• chr15-90411783-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQGAP1	NM_003870.4	c.156-14327G>A		intron_variant		ENST00000268182.10	NP_003861.1
IQGAP1	XM_047433204.1	c.156-14327G>A		intron_variant			XP_047289160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQGAP1	ENST00000268182.10	c.156-14327G>A		intron_variant		1	NM_003870.4	ENSP00000268182	P1
IQGAP1	ENST00000560418.1	c.-309-14327G>A		intron_variant		5		ENSP00000452723
IQGAP1	ENST00000560738.1	c.106+20959G>A		intron_variant		5		ENSP00000453181
IQGAP1	ENST00000633485.1	c.156-14327G>A		intron_variant, NMD_transcript_variant		5		ENSP00000488618

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

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.362

Alfa AF: 0.331 Hom.: 16109

Bravo AF: 0.373

Asia WGS AF: 0.561 AC: 1951 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs2589949; hg19: chr15-90955015;