Variant 2-105272937-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004257.6(TGFBRAP1):c.1890G>A(p.Lys630=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,611,686 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 60 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 41 hom. )

Consequence

TGFBRAP1
NM_004257.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0100

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 2-105272937-C-T is Benign according to our data. Variant chr2-105272937-C-T is described in ClinVar as [Benign]. Clinvar id is 786864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.01 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1912/151466) while in subpopulation AFR AF= 0.0444 (1833/41272). AF 95% confidence interval is 0.0427. There are 60 homozygotes in gnomad4. There are 886 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1912 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBRAP1	NM_004257.6 linkuse as main transcript	c.1890G>A	p.Lys630=	synonymous_variant	10/12	ENST00000393359.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBRAP1	ENST00000393359.7 linkuse as main transcript	c.1890G>A	p.Lys630=	synonymous_variant	10/12	1	NM_004257.6	P1
TGFBRAP1	ENST00000595531.5 linkuse as main transcript	c.1890G>A	p.Lys630=	synonymous_variant	9/11	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1912

AN:

151346

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0445

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00388

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000737

Gnomad OTH

AF:

0.00721

GnomAD3 exomes

AF:

0.00347

AC:

869

AN:

250706

Hom.:

AF XY:

0.00257

AC XY:

349

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.0468

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.00130

AC:

1903

AN:

1460220

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

823

AN XY:

726476

show subpopulations

Gnomad4 AFR exome

AF:

0.0457

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.00275

GnomAD4 genome

AF:

0.0126

AC:

1912

AN:

151466

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

886

AN XY:

74040

show subpopulations

Gnomad4 AFR

AF:

0.0444

Gnomad4 AMR

AF:

0.00388

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000737

Gnomad4 OTH

AF:

0.00714

Alfa

AF:

0.00770

Hom.:

Bravo

AF:

0.0143

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.82

DANN

Benign

0.41

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