rs1042538

Positions:

• chr15-90501176-T-A
• chr15-90501176-T-C
• chr15-90501176-T-G

Variant summary

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

The NM_003870.4(IQGAP1):​c.*1068T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,416 control chromosomes in the GnomAD database, including 55,501 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 0.85 (55355 hom., cov: 31)
  • Exomes 𝑓: 0.83 (146 hom.)
• Consequence: IQGAP1 NM_003870.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.724

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 (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQGAP1	NM_003870.4	c.*1068T>A		3_prime_UTR_variant	38/38	ENST00000268182.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQGAP1	ENST00000268182.10	c.*1068T>A		3_prime_UTR_variant	38/38	1	NM_003870.4	P1
IQGAP1	ENST00000558957.1	n.2100T>A		non_coding_transcript_exon_variant	3/3	2
IQGAP1	ENST00000561086.1	n.1809T>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128809 AN: 151880 Hom.: 55315 Cov.: 31

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.845

GnomAD4 exome AF: 0.833 AC: 348 AN: 418 Hom.: 146 Cov.: 0 AF XY: 0.835 AC XY: 212 AN XY: 254

Gnomad4 FIN exome AF: 0.837

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.848 AC: 128892 AN: 151998 Hom.: 55355 Cov.: 31 AF XY: 0.841 AC XY: 62500 AN XY: 74290

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.874

Gnomad4 OTH AF: 0.844

Alfa AF: 0.867 Hom.: 6724

Bravo AF: 0.836

Asia WGS AF: 0.681 AC: 2366 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.5
DANN	Benign	0.74

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: rs1042538; hg19: chr15-91044408;