15-90431158-G-C

Position:

• chr15-90431158-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQGAP1	NM_003870.4	c.390+1492G>C		intron_variant		ENST00000268182.10	NP_003861.1
IQGAP1	XM_047433204.1	c.390+1492G>C		intron_variant			XP_047289160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQGAP1	ENST00000268182.10	c.390+1492G>C		intron_variant		1	NM_003870.4	ENSP00000268182.5
IQGAP1	ENST00000560738.1	c.107-34889G>C		intron_variant		5		ENSP00000453181.1
IQGAP1	ENST00000560418.1	c.-74-63G>C		intron_variant		5		ENSP00000452723.1
IQGAP1	ENST00000633485.1	n.390+1492G>C		intron_variant		5		ENSP00000488618.1

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

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.540

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.38

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: rs8035980; hg19: chr15-90974390;