15-90434101-G-T

Variant names:

• chr15-90434101-G-T
• rs8042861
• NM_003870.4:c.467+306G>T

Variant summary

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

The NM_003870.4(IQGAP1):​c.467+306G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,782 control chromosomes in the GnomAD database, including 27,532 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 0.58 (27532 hom., cov: 31)
• Consequence: IQGAP1 NM_003870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 27 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQGAP1	NM_003870.4	c.467+306G>T		intron_variant	Intron 5 of 37	ENST00000268182.10	NP_003861.1
IQGAP1	XM_047433204.1	c.467+306G>T		intron_variant	Intron 5 of 29		XP_047289160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQGAP1	ENST00000268182.10	c.467+306G>T		intron_variant	Intron 5 of 37	1	NM_003870.4	ENSP00000268182.5
IQGAP1	ENST00000560738.1	c.107-31946G>T		intron_variant	Intron 2 of 24	5		ENSP00000453181.1
IQGAP1	ENST00000560418.1	c.35+306G>T		intron_variant	Intron 5 of 6	5		ENSP00000452723.1
IQGAP1	ENST00000633485.1	n.467+306G>T		intron_variant	Intron 5 of 38	5		ENSP00000488618.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87913 AN: 151664 Hom.: 27479 Cov.: 31

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.580 AC: 88027 AN: 151782 Hom.: 27532 Cov.: 31 AF XY: 0.581 AC XY: 43117 AN XY: 74176

African (AFR) AF: 0.798 AC: 33017 AN: 41370

American (AMR) AF: 0.614 AC: 9355 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1434 AN: 3464

East Asian (EAS) AF: 0.830 AC: 4293 AN: 5174

South Asian (SAS) AF: 0.601 AC: 2888 AN: 4804

European-Finnish (FIN) AF: 0.447 AC: 4696 AN: 10512

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30567 AN: 67920

Other (OTH) AF: 0.553 AC: 1164 AN: 2106

Alfa AF: 0.471 Hom.: 11302

Bravo AF: 0.609

Asia WGS AF: 0.699 AC: 2433 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	0.85
DANN	Benign	0.63
PhyloP100		-0.29
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: rs8042861; hg19: chr15-90977333;