Genetic Variant IQGAP1:c.4629-645G>A (chr15-90494068-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003870.4(IQGAP1):c.4629-645G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,982 control chromosomes in the GnomAD database, including 26,656 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 0.57 ( 26656 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

IQGAP1
NM_003870.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.99

Publications

8 publications found

Variant links:

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]

IQGAP1 links:

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ACMG classification

Classification was made for transcript

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 = 0.83 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQGAP1	NM_003870.4	MANE Select	c.4629-645G>A		intron	N/A	NP_003861.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IQGAP1	ENST00000268182.10	TSL:1 MANE Select	c.4629-645G>A	intron	N/A	ENSP00000268182.5
IQGAP1	ENST00000558957.1	TSL:2	n.42G>A	non_coding_transcript_exon	Exon 1 of 3
IQGAP1	ENST00000560738.1	TSL:5	c.2913-645G>A	intron	N/A	ENSP00000453181.1

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

87058

AN:

151848

Hom.:

26614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.758

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.631

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.452

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.545

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.214

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.286

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.574

AC:

87154

AN:

151966

Hom.:

26656

Cov.:

AF XY:

0.576

AC XY:

42757

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.758

AC:

31408

AN:

41448

American (AMR)

AF:

0.632

AC:

9649

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

1419

AN:

3462

East Asian (EAS)

AF:

0.851

AC:

4409

AN:

5182

South Asian (SAS)

AF:

0.609

AC:

2933

AN:

4820

European-Finnish (FIN)

AF:

0.452

AC:

4742

AN:

10490

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30824

AN:

67970

Other (OTH)

AF:

0.547

AC:

1154

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1748

3496

5243

6991

8739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.448

Hom.:

2169

Bravo

AF:

0.601

Asia WGS

AF:

0.718

AC:

2497

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.019

(source)

DANN

Benign

0.21

PhyloP100

-5.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over