Variant 2-105269692-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004257.6(TGFBRAP1):c.1986A>C(p.Gly662Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00763 in 1,546,164 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 60 hom. )

Consequence

TGFBRAP1
NM_004257.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0690

Variant links:

Genes affected

TGFBRAP1 (HGNC:16836): (transforming growth factor beta receptor associated protein 1) This gene encodes a protein that binds to transforming growth factor-beta (TGF-beta) receptors and plays a role in TGF-beta signaling. The encoded protein acts as a chaprone in signaling downstream of TGF-beta. It is involved in signal-dependent association with SMAD4. The protein is also a component of mammalian CORVET, a multisubunit tethering protein complex that is involved in fusion of early endosomes. [provided by RefSeq, Jun 2016]

TGFBRAP1 links:

TGFBRAP1 (HGNC:):

TGFBRAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-105269692-T-G is Benign according to our data. Variant chr2-105269692-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2651227.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.069 with no splicing effect.

BS2

High AC in GnomAd4 at 804 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBRAP1	NM_004257.6 linkuse as main transcript	c.1986A>C	p.Gly662Gly	synonymous_variant	11/12	ENST00000393359.7	NP_004248.2	Q8WUH2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBRAP1	ENST00000393359.7 linkuse as main transcript	c.1986A>C	p.Gly662Gly	synonymous_variant	11/12	1	NM_004257.6	ENSP00000377027.2		Q8WUH2
TGFBRAP1	ENST00000595531.5 linkuse as main transcript	c.1986A>C	p.Gly662Gly	synonymous_variant	10/11	1		ENSP00000471434.2		Q8WUH2

Frequencies

GnomAD3 genomes

AF:

0.00529

AC:

804

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00496

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00906

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00592

AC:

1189

AN:

200906

Hom.:

AF XY:

0.00606

AC XY:

655

AN XY:

108016

show subpopulations

Gnomad AFR exome

AF:

0.00159

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.00224

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00459

Gnomad FIN exome

AF:

0.00389

Gnomad NFE exome

AF:

0.00972

Gnomad OTH exome

AF:

0.00752

GnomAD4 exome

AF:

0.00788

AC:

10986

AN:

1393954

Hom.:

Cov.:

AF XY:

0.00782

AC XY:

5350

AN XY:

684100

show subpopulations

Gnomad4 AFR exome

AF:

0.00124

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.00179

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00445

Gnomad4 FIN exome

AF:

0.00409

Gnomad4 NFE exome

AF:

0.00925

Gnomad4 OTH exome

AF:

0.00608

GnomAD4 genome

AF:

0.00528

AC:

804

AN:

152210

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.00906

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00611

Hom.:

Bravo

AF:

0.00512

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

TGFBRAP1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.040

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

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