chr19-41353117-C-T

Variant names:

• chr19-41353117-C-T
• rs56155294
• NM_000660.7:c.-73G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS1

The NM_000660.7(TGFB1):​c.-73G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000796 in 1,431,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00048 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (0 hom.)
• Consequence: TGFB1 NM_000660.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• Publications: 3 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00048 (73/152004) while in subpopulation NFE AF = 0.000913 (62/67900). AF 95% confidence interval is 0.00073. There are 0 homozygotes in GnomAd4. There are 29 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFB1	NM_000660.7	MANE Select	c.-73G>A		5_prime_UTR	Exon 1 of 7	NP_000651.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFB1	ENST00000221930.6	TSL:1 MANE Select	c.-73G>A		5_prime_UTR	Exon 1 of 7	ENSP00000221930.4
	TMEM91	ENST00000539627.5	TSL:1	c.-30+1915C>T		intron	N/A	ENSP00000441900.1
	ENSG00000255730	ENST00000604424.1	TSL:4	n.350+1915C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000481 AC: 73 AN: 151886 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000913

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000834 AC: 1067 AN: 1279376 Hom.: 0 Cov.: 32 AF XY: 0.000824 AC XY: 512 AN XY: 621224

African (AFR) AF: 0.000223 AC: 6 AN: 26868

American (AMR) AF: 0.000150 AC: 3 AN: 19998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18592

East Asian (EAS) AF: 0.00 AC: 0 AN: 32842

South Asian (SAS) AF: 0.00 AC: 0 AN: 62578

European-Finnish (FIN) AF: 0.0000332 AC: 1 AN: 30082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3804

European-Non Finnish (NFE) AF: 0.000959 AC: 989 AN: 1031430

Other (OTH) AF: 0.00128 AC: 68 AN: 53182

GnomAD4 genome AF: 0.000480 AC: 73 AN: 152004 Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74320

African (AFR) AF: 0.000193 AC: 8 AN: 41502

American (AMR) AF: 0.000131 AC: 2 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000913 AC: 62 AN: 67900

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000416 Hom.: 0

Bravo AF: 0.000431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.97
PhyloP100		-0.76
PromoterAI		0.038	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4
Mutation Taster		=299/1	polymorphism

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: rs56155294; hg19: chr19-41859022;