NM_000660.7:c.-762dupC

Variant names:

• chr19-41353805-C-CG
• rs1799753
• NM_000660.7:c.-762dupC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.56
• Publications: 1 publications found

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]

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]

ENSG00000255730 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000660.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFB1	NM_000660.7	MANE Select	c.-762dupC		5_prime_UTR	Exon 1 of 7	NP_000651.3	P01137

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFB1	ENST00000221930.6	TSL:1 MANE Select	c.-762dupC		5_prime_UTR	Exon 1 of 7	ENSP00000221930.4	A0A499FJK2
	TMEM91	ENST00000539627.5	TSL:1	c.-30+2610dupG		intron	N/A	ENSP00000441900.1	F5GWC9
	TGFB1	ENST00000890114.1		c.-762dupC		5_prime_UTR	Exon 1 of 7	ENSP00000560173.1

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9455 AN: 151254 Hom.: 351 Cov.: 30

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: 39 AN: 886 Hom.: 1 Cov.: 0 AF XY: 0.0403 AC XY: 20 AN XY: 496

African (AFR) AF: 0.0556 AC: 2 AN: 36

American (AMR) AF: 0.00 AC: 0 AN: 16

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 42

East Asian (EAS) AF: 0.00 AC: 0 AN: 58

South Asian (SAS) AF: 0.00 AC: 0 AN: 12

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0542 AC: 35 AN: 646

Other (OTH) AF: 0.0435 AC: 2 AN: 46

GnomAD4 genome AF: 0.0625 AC: 9461 AN: 151360 Hom.: 353 Cov.: 30 AF XY: 0.0602 AC XY: 4455 AN XY: 74002

African (AFR) AF: 0.0640 AC: 2644 AN: 41312

American (AMR) AF: 0.0405 AC: 618 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3468

East Asian (EAS) AF: 0.00177 AC: 9 AN: 5096

South Asian (SAS) AF: 0.0751 AC: 361 AN: 4810

European-Finnish (FIN) AF: 0.0307 AC: 324 AN: 10542

Middle Eastern (MID) AF: 0.0590 AC: 17 AN: 288

European-Non Finnish (NFE) AF: 0.0769 AC: 5194 AN: 67564

Other (OTH) AF: 0.0542 AC: 114 AN: 2104

Alfa AF: 0.0288 Hom.: 20

Bravo AF: 0.0622

Asia WGS AF: 0.0270 AC: 94 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=289/11	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1799753; hg19: chr19-41859710;