dbSNP rs1800999: TGFB1:c.-762dupC (chr19-41353805-C-CG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000660.7(TGFB1):c.-762dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0624 in 152,246 control chromosomes in the GnomAD database, including 354 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.063 ( 353 hom., cov: 30)

Exomes 𝑓: 0.044 ( 1 hom. )

Consequence

TGFB1
NM_000660.7 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.56

Variant links:

Genes affected

TGFB1 (HGNC:11766): (transforming growth factor beta 1) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGFB family members. This encoded protein regulates cell proliferation, differentiation and growth, and can modulate expression and activation of other growth factors including interferon gamma and tumor necrosis factor alpha. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease. [provided by RefSeq, Aug 2016]

TGFB1 links:

TMEM91 (HGNC:32393): (transmembrane protein 91) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle and membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM91 links:

ENSG00000255730 (HGNC:):

ENSG00000255730 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 19-41353805-C-CG is Benign according to our data. Variant chr19-41353805-C-CG is described in ClinVar as [Benign]. Clinvar id is 1180304.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFB1	NM_000660.7 link	c.-762dupC		5_prime_UTR_variant	Exon 1 of 7	ENST00000221930.6	NP_000651.3	P01137A0A499FJK2
TGFB1	XM_011527242.3 link	c.-762dupC		5_prime_UTR_variant	Exon 1 of 7		XP_011525544.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TGFB1	ENST00000221930.6 link	c.-762dupC	5_prime_UTR_variant	Exon 1 of 7	1	NM_000660.7	ENSP00000221930.4	A0A499FJK2
TMEM91	ENST00000539627.5 link	c.-30+2610dupG	intron_variant	Intron 1 of 2	1		ENSP00000441900.1	F5GWC9
ENSG00000255730	ENST00000604424.1 link	n.350+2610dupG	intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes

AF:

0.0625

AC:

9455

AN:

151254

Hom.:

351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0642

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.0405

Gnomad ASJ

AF:

0.0438

Gnomad EAS

AF:

0.00176

Gnomad SAS

AF:

0.0740

Gnomad FIN

AF:

0.0307

Gnomad MID

AF:

0.0548

Gnomad NFE

AF:

0.0769

Gnomad OTH

AF:

0.0548

GnomAD4 exome

AF:

0.0440

AC:

AN:

886

Hom.:

Cov.:

AF XY:

0.0403

AC XY:

AN XY:

496

show subpopulations

Gnomad4 AFR exome

AF:

0.0556

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0542

Gnomad4 OTH exome

AF:

0.0435

GnomAD4 genome

AF:

0.0625

AC:

9461

AN:

151360

Hom.:

353

Cov.:

AF XY:

0.0602

AC XY:

4455

AN XY:

74002

show subpopulations

Gnomad4 AFR

AF:

0.0640

Gnomad4 AMR

AF:

0.0405

Gnomad4 ASJ

AF:

0.0438

Gnomad4 EAS

AF:

0.00177

Gnomad4 SAS

AF:

0.0751

Gnomad4 FIN

AF:

0.0307

Gnomad4 NFE

AF:

0.0769

Gnomad4 OTH

AF:

0.0542

Bravo

AF:

0.0622

Asia WGS

AF:

0.0270

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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