rs1978151

Positions:

• chr15-90494068-G-A
• chr15-90494068-G-C
• chr15-90494068-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.4629-645G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,982 control chromosomes in the GnomAD database, including 26,656 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 0.57 (26656 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: IQGAP1 NM_003870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.99

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]

IQGAP1 (HGNC:):

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 = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQGAP1	NM_003870.4	c.4629-645G>A		intron_variant		ENST00000268182.10	NP_003861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQGAP1	ENST00000268182.10	c.4629-645G>A		intron_variant		1	NM_003870.4	ENSP00000268182.5

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87058 AN: 151848 Hom.: 26614 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.250 AC: 4 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.214 AC XY: 3 AN XY: 14

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.574 AC: 87154 AN: 151966 Hom.: 26656 Cov.: 32 AF XY: 0.576 AC XY: 42757 AN XY: 74248

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.547

Alfa AF: 0.433 Hom.: 1936

Bravo AF: 0.601

Asia WGS AF: 0.718 AC: 2497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.019
DANN	Benign	0.21

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: rs1978151; hg19: chr15-91037300;