15-90495062-T-C

Position:

• chr15-90495062-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQGAP1	NM_003870.4	c.4751+227T>C		intron_variant		ENST00000268182.10	NP_003861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQGAP1	ENST00000268182.10	c.4751+227T>C		intron_variant		1	NM_003870.4	ENSP00000268182.5
IQGAP1	ENST00000560738.1	c.3035+227T>C		intron_variant		5		ENSP00000453181.1
IQGAP1	ENST00000558957.1	n.809+227T>C		intron_variant		2
IQGAP1	ENST00000633485.1	n.*1223+227T>C		intron_variant		5		ENSP00000488618.1

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

Gnomad4 AFR AF: 0.0973

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.0988

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.161

Alfa AF: 0.151 Hom.: 1106

Bravo AF: 0.170

Asia WGS AF: 0.323 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.53

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: rs16944523; hg19: chr15-91038294;