Variant chr21-31120713-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_001353694.2(TIAM1):c.4431T>C(p.Gly1477=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,613,596 control chromosomes in the GnomAD database, including 190,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.50 ( 19555 hom., cov: 31)

Exomes 𝑓: 0.48 ( 171294 hom. )

Consequence

TIAM1
NM_001353694.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0500

Variant links:

Genes affected

TIAM1 (HGNC:11805): (TIAM Rac1 associated GEF 1) This gene encodes a RAC1-specific guanine nucleotide exchange factor (GEF). GEFs mediate the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP). The binding of GTP induces a conformational change in RAC1 that allows downstream effectors to bind and transduce a signal. This gene thus regulates RAC1 signaling pathways that affect cell shape, migration, adhesion, growth, survival, and polarity, as well as influencing actin cytoskeletal formation, endocytosis, and membrane trafficking. This gene thus plays an important role in cell invasion, metastasis, and carcinogenesis. In addition to RAC1, the encoded protein activates additional Rho-like GTPases such as CDC42, RAC2, RAC3 and RHOA. This gene encodes multiple protein isoforms that experience a diverse array of intramolecular, protein-protein, and phosphorylation interactions as well as phosphoinositide binding. Both the longer and shorter isoforms have C-terminal Dbl homology (DH) and pleckstrin homology (PH) domains while only the longer isoforms of this gene have the N-terminal myristoylation site and the downstream N-terminal PH domain, ras-binding domain (RBD), and PSD-95/DlgA/ZO-1 (PDZ) domain. [provided by RefSeq, Jul 2017]

TIAM1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 21-31120713-A-G is Benign according to our data. Variant chr21-31120713-A-G is described in ClinVar as [Benign]. Clinvar id is 3059045.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIAM1	NM_001353694.2 linkuse as main transcript	c.4431T>C	p.Gly1477=	synonymous_variant	28/28	ENST00000541036.6	NP_001340623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIAM1	ENST00000541036.6 linkuse as main transcript	c.4431T>C	p.Gly1477=	synonymous_variant	28/28	5	NM_001353694.2	ENSP00000441570	P1	Q13009-1

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76206

AN:

151656

Hom.:

19544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.567

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.753

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.466

Gnomad OTH

AF:

0.501

GnomAD3 exomes

AF:

0.509

AC:

127926

AN:

251240

Hom.:

34307

AF XY:

0.492

AC XY:

66815

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.531

Gnomad AMR exome

AF:

0.638

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.772

Gnomad SAS exome

AF:

0.332

Gnomad FIN exome

AF:

0.551

Gnomad NFE exome

AF:

0.473

Gnomad OTH exome

AF:

0.490

GnomAD4 exome

AF:

0.479

AC:

699695

AN:

1461824

Hom.:

171294

Cov.:

AF XY:

0.473

AC XY:

343656

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.532

Gnomad4 AMR exome

AF:

0.631

Gnomad4 ASJ exome

AF:

0.419

Gnomad4 EAS exome

AF:

0.740

Gnomad4 SAS exome

AF:

0.337

Gnomad4 FIN exome

AF:

0.554

Gnomad4 NFE exome

AF:

0.471

Gnomad4 OTH exome

AF:

0.483

GnomAD4 genome

AF:

0.502

AC:

76256

AN:

151772

Hom.:

19555

Cov.:

AF XY:

0.505

AC XY:

37447

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.522

Gnomad4 AMR

AF:

0.568

Gnomad4 ASJ

AF:

0.432

Gnomad4 EAS

AF:

0.752

Gnomad4 SAS

AF:

0.355

Gnomad4 FIN

AF:

0.551

Gnomad4 NFE

AF:

0.466

Gnomad4 OTH

AF:

0.499

Alfa

AF:

0.472

Hom.:

32535

Bravo

AF:

0.514

Asia WGS

AF:

0.521

AC:

1814

AN:

3478

EpiCase

AF:

0.465

EpiControl

AF:

0.459

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TIAM1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 20, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

3.9

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over