15-90425745-T-C

Variant names:

• chr15-90425745-T-C
• rs2657947
• NM_003870.4:c.156-365T>C

Variant summary

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

The NM_003870.4(IQGAP1):​c.156-365T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,098 control chromosomes in the GnomAD database, including 26,888 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 (26888 hom., cov: 32)
• Consequence: IQGAP1 NM_003870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQGAP1	NM_003870.4	c.156-365T>C		intron_variant	Intron 2 of 37	ENST00000268182.10	NP_003861.1
IQGAP1	XM_047433204.1	c.156-365T>C		intron_variant	Intron 2 of 29		XP_047289160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQGAP1	ENST00000268182.10	c.156-365T>C		intron_variant	Intron 2 of 37	1	NM_003870.4	ENSP00000268182.5
IQGAP1	ENST00000560738.1	c.106+34921T>C		intron_variant	Intron 2 of 24	5		ENSP00000453181.1
IQGAP1	ENST00000560418.1	c.-309-365T>C		intron_variant	Intron 1 of 6	5		ENSP00000452723.1
IQGAP1	ENST00000633485.1	n.156-365T>C		intron_variant	Intron 2 of 38	5		ENSP00000488618.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87278 AN: 151980 Hom.: 26851 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.574 AC: 87367 AN: 152098 Hom.: 26888 Cov.: 32 AF XY: 0.576 AC XY: 42855 AN XY: 74340

African (AFR) AF: 0.772 AC: 32036 AN: 41496

American (AMR) AF: 0.630 AC: 9630 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1437 AN: 3472

East Asian (EAS) AF: 0.829 AC: 4293 AN: 5180

South Asian (SAS) AF: 0.602 AC: 2905 AN: 4822

European-Finnish (FIN) AF: 0.447 AC: 4715 AN: 10556

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30583 AN: 67980

Other (OTH) AF: 0.547 AC: 1155 AN: 2112

Alfa AF: 0.448 Hom.: 2181

Bravo AF: 0.603

Asia WGS AF: 0.694 AC: 2414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.83
DANN	Benign	0.66
PhyloP100		-0.23
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: rs2657947; hg19: chr15-90968977;