Variant rs1800471 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000660.7(TGFB1):c.74G>C(p.Arg25Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 152132 control chromosomes in the gnomAD Genomes database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R25G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.063 ( 354 hom., cov: 32)

Exomes 𝑓: 0.056 ( 245 hom. )

Consequence

TGFB1
NM_000660.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.754

Links

TGFB1 (HGNC:11766):

TMEM91 (HGNC:32393):

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002168864).

BP6

Variant 19-41352971-C-G is Benign according to our data. Variant chr19-41352971-C-G is described in ClinVar as [Benign]. Clinvar id is 38902. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-41352971-C-G is described in Lovd as [Likely_benign].

BA1

GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFB1	NM_000660.7 linkuse as main transcript	c.74G>C	p.Arg25Pro	missense_variant	1/7	ENST00000221930.6
TGFB1	XM_011527242.3 linkuse as main transcript	c.74G>C	p.Arg25Pro	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TGFB1	ENST00000221930.6 linkuse as main transcript	c.74G>C	p.Arg25Pro	missense_variant	1/7	1	NM_000660.7	P1
TMEM91	ENST00000539627.5 linkuse as main transcript	c.-30+1769C>G		intron_variant		1
TGFB1	ENST00000600196.2 linkuse as main transcript	c.74G>C	p.Arg25Pro	missense_variant	1/6	5
TGFB1	ENST00000677934.1 linkuse as main transcript	c.74G>C	p.Arg25Pro	missense_variant	1/5

Frequencies

GnomAD3 genomes

AF:

0.0630

AC:

9580

AN:

152132

Hom.:

354

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0647

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0407

Gnomad ASJ

AF:

0.0435

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0750

Gnomad FIN

AF:

0.0310

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0775

Gnomad OTH

AF:

0.0550

GnomAD3 exomes

AF:

0.0565

AC:

8035

AN:

142282

Hom.:

245

AF XY:

0.0592

AC XY:

4571

AN XY:

77192

show subpopulations

Gnomad AFR exome

AF:

0.0649

Gnomad AMR exome

AF:

0.0341

Gnomad ASJ exome

AF:

0.0401

Gnomad EAS exome

AF:

0.000818

Gnomad SAS exome

AF:

0.0783

Gnomad FIN exome

AF:

0.0347

Gnomad NFE exome

AF:

0.0732

Gnomad OTH exome

AF:

0.0571

GnomAD4 exome

AF:

0.0719

AC:

100121

AN:

1391618

Hom.:

3846

AF XY:

0.0717

AC XY:

49252

AN XY:

687184

show subpopulations

Gnomad4 AFR exome

AF:

0.0623

Gnomad4 AMR exome

AF:

0.0369

Gnomad4 ASJ exome

AF:

0.0412

Gnomad4 EAS exome

AF:

0.000390

Gnomad4 SAS exome

AF:

0.0759

Gnomad4 FIN exome

AF:

0.0394

Gnomad4 NFE exome

AF:

0.0777

Gnomad4 OTH exome

AF:

0.0662

Alfa

AF:

0.0554

Hom.:

Bravo

AF:

0.0629

TwinsUK

AF:

0.0798

AC:

296

ALSPAC

AF:

0.0838

AC:

323

ESP6500AA

AF:

0.0454

AC:

187

ESP6500EA

AF:

0.0491

AC:

396

ExAC

AF:

0.0264

AC:

2615

Asia WGS

AF:

0.0300

AC:

104

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, PreventionGenetics

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.55

Cadd

Benign

Dann

Uncertain

0.97

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.50

REVEL

Benign

0.067

Sift

Benign

0.25

Sift4G

Benign

0.28

Vest4

0.16

MPC

2.0

ClinPred

0.018

GERP RS

2.8

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over