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GeneBe

15-90441630-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_003870.4(IQGAP1):c.774C>T(p.Tyr258=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,613,694 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00083 ( 5 hom. )

Consequence

IQGAP1
NM_003870.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.05
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-90441630-C-T is Benign according to our data. Variant chr15-90441630-C-T is described in ClinVar as [Benign]. Clinvar id is 714664.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.05 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00542 (824/152162) while in subpopulation AFR AF= 0.0175 (726/41502). AF 95% confidence interval is 0.0164. There are 5 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 822 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IQGAP1NM_003870.4 linkuse as main transcriptc.774C>T p.Tyr258= synonymous_variant 8/38 ENST00000268182.10
IQGAP1XM_047433204.1 linkuse as main transcriptc.774C>T p.Tyr258= synonymous_variant 8/30

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IQGAP1ENST00000268182.10 linkuse as main transcriptc.774C>T p.Tyr258= synonymous_variant 8/381 NM_003870.4 P1
IQGAP1ENST00000560738.1 linkuse as main transcriptc.107-24417C>T intron_variant 5
IQGAP1ENST00000633485.1 linkuse as main transcriptc.774C>T p.Tyr258= synonymous_variant, NMD_transcript_variant 8/395

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00541
AC:
822
AN:
152044
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0175
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00321
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00955
Gnomad NFE
AF:
0.000573
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00178
AC:
447
AN:
251112
Hom.:
1
AF XY:
0.00137
AC XY:
186
AN XY:
135706
show subpopulations
Gnomad AFR exome
AF:
0.0172
Gnomad AMR exome
AF:
0.00278
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000529
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.000828
AC:
1210
AN:
1461532
Hom.:
5
Cov.:
32
AF XY:
0.000736
AC XY:
535
AN XY:
727092
show subpopulations
Gnomad4 AFR exome
AF:
0.0172
Gnomad4 AMR exome
AF:
0.00286
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000324
Gnomad4 OTH exome
AF:
0.00205
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00542
AC:
824
AN:
152162
Hom.:
5
Cov.:
32
AF XY:
0.00500
AC XY:
372
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.0175
Gnomad4 AMR
AF:
0.00327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000573
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00338
Hom.:
0
Bravo
AF:
0.00669
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000545
EpiControl
AF:
0.000533

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
Cadd
Benign
8.7
Dann
Benign
0.45
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs114889611; hg19: chr15-90984862; API