rs3213649

Positions:

• chr15-90455896-A-C
• chr15-90455896-A-G
• chr15-90455896-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003870.4(IQGAP1):​c.1613-256A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,186 control chromosomes in the GnomAD database, including 2,590 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 0.18 (2590 hom., cov: 32)
• Consequence: IQGAP1 NM_003870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQGAP1	NM_003870.4	c.1613-256A>C		intron_variant		ENST00000268182.10
IQGAP1	XM_047433204.1	c.1613-256A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQGAP1	ENST00000268182.10	c.1613-256A>C		intron_variant		1	NM_003870.4	P1
IQGAP1	ENST00000560738.1	c.107-10151A>C		intron_variant		5
IQGAP1	ENST00000633485.1	c.1613-256A>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27475 AN: 152068 Hom.: 2580 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.181 AC: 27504 AN: 152186 Hom.: 2590 Cov.: 32 AF XY: 0.181 AC XY: 13432 AN XY: 74406

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.185

Alfa AF: 0.168 Hom.: 1113

Bravo AF: 0.175

Asia WGS AF: 0.246 AC: 855 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.20
DANN	Benign	0.80

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: rs3213649; hg19: chr15-90999128;