chr15-90495062-T-C

Variant names:

• chr15-90495062-T-C
• rs16944523
• NM_003870.4:c.4751+227T>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.4751+227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,274 control chromosomes in the GnomAD database, including 2,623 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 0.16 (2623 hom., cov: 32)
• Consequence: IQGAP1 NM_003870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.481
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQGAP1	NM_003870.4	MANE Select	c.4751+227T>C		intron	N/A	NP_003861.1	P46940

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQGAP1	ENST00000268182.10	TSL:1 MANE Select	c.4751+227T>C		intron	N/A	ENSP00000268182.5	P46940
	IQGAP1	ENST00000921154.1		c.4748+227T>C		intron	N/A	ENSP00000591213.1
	IQGAP1	ENST00000921153.1		c.4502+227T>C		intron	N/A	ENSP00000591212.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23634 AN: 152156 Hom.: 2604 Cov.: 32

Gnomad AFR AF: 0.0972

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.155 AC: 23672 AN: 152274 Hom.: 2623 Cov.: 32 AF XY: 0.162 AC XY: 12096 AN XY: 74470

African (AFR) AF: 0.0973 AC: 4045 AN: 41564

American (AMR) AF: 0.324 AC: 4958 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 343 AN: 3472

East Asian (EAS) AF: 0.461 AC: 2385 AN: 5176

South Asian (SAS) AF: 0.284 AC: 1370 AN: 4826

European-Finnish (FIN) AF: 0.143 AC: 1512 AN: 10608

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8611 AN: 68020

Other (OTH) AF: 0.161 AC: 341 AN: 2114

Alfa AF: 0.149 Hom.: 1187

Bravo AF: 0.170

Asia WGS AF: 0.323 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.53
PhyloP100		0.48
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: rs16944523; hg19: chr15-91038294;