rs11466315

Variant names:

• chr19-41353871-C-G
• rs11466315
• NM_000660.7:c.-827G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000660.7(TGFB1):​c.-827G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 168,742 control chromosomes in the GnomAD database, including 42 homozygotes. 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 0.013 (41 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (1 hom.)
• Consequence: TGFB1 NM_000660.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1941/151660) while in subpopulation AFR AF = 0.0448 (1854/41428). AF 95% confidence interval is 0.0431. There are 41 homozygotes in GnomAd4. There are 909 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 AD,AR gene

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.-827G>C		5_prime_UTR	Exon 1 of 7	NP_000651.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFB1	ENST00000221930.6	TSL:1 MANE Select	c.-827G>C		5_prime_UTR	Exon 1 of 7	ENSP00000221930.4
	TMEM91	ENST00000539627.5	TSL:1	c.-30+2669C>G		intron	N/A	ENSP00000441900.1
	TGFB1	ENST00000890114.1		c.-827G>C		5_prime_UTR	Exon 1 of 7	ENSP00000560173.1

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1931 AN: 151552 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0446

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00453

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000625

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000886

Gnomad OTH AF: 0.00432

GnomAD4 exome AF: 0.00176 AC: 30 AN: 17082 Hom.: 1 Cov.: 0 AF XY: 0.00149 AC XY: 13 AN XY: 8722

African (AFR) AF: 0.0406 AC: 26 AN: 640

American (AMR) AF: 0.00233 AC: 1 AN: 430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 612

East Asian (EAS) AF: 0.00 AC: 0 AN: 1166

South Asian (SAS) AF: 0.00 AC: 0 AN: 292

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 78

European-Non Finnish (NFE) AF: 0.0000867 AC: 1 AN: 11538

Other (OTH) AF: 0.00172 AC: 2 AN: 1164

GnomAD4 genome AF: 0.0128 AC: 1941 AN: 151660 Hom.: 41 Cov.: 32 AF XY: 0.0123 AC XY: 909 AN XY: 74092

African (AFR) AF: 0.0448 AC: 1854 AN: 41428

American (AMR) AF: 0.00452 AC: 69 AN: 15262

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5102

South Asian (SAS) AF: 0.000625 AC: 3 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

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

European-Non Finnish (NFE) AF: 0.0000886 AC: 6 AN: 67736

Other (OTH) AF: 0.00427 AC: 9 AN: 2106

Alfa AF: 0.0105 Hom.: 5

Bravo AF: 0.0145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		0.57
PromoterAI		0.026	Neutral
Mutation Taster		=298/2	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: rs11466315; hg19: chr19-41859776;