rs11466334

chr19-41341832-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000660.7(TGFB1):c.860+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00447 in 1,610,914 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (133 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (143 hom.)
• Consequence: TGFB1 NM_000660.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-41341832-G-A is Benign according to our data. Variant chr19-41341832-G-A is described in ClinVar as [Benign]. Clinvar id is 1261994.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFB1	NM_000660.7	c.860+51C>T		intron_variant		ENST00000221930.6
TGFB1	XM_011527242.3	c.863+51C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFB1	ENST00000221930.6	c.860+51C>T		intron_variant		1	NM_000660.7	P1
TGFB1	ENST00000600196.2	c.712+338C>T		intron_variant		5
TGFB1	ENST00000677934.1	c.634+2915C>T		intron_variant
TGFB1	ENST00000598758.5	n.148+51C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3483 AN: 152184 Hom.: 131 Cov.: 31

Gnomad AFR AF: 0.0786

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00963

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00590 AC: 1469 AN: 249192 Hom.: 48 AF XY: 0.00441 AC XY: 595 AN XY: 134914

Gnomad AFR exome AF: 0.0774

Gnomad AMR exome AF: 0.00400

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000366

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00254 AC: 3710 AN: 1458612 Hom.: 143 Cov.: 32 AF XY: 0.00223 AC XY: 1615 AN XY: 725700

Gnomad4 AFR exome AF: 0.0835

Gnomad4 AMR exome AF: 0.00452

Gnomad4 ASJ exome AF: 0.00168

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000295

Gnomad4 OTH exome AF: 0.00499

GnomAD4 genome AF: 0.0229 AC: 3495 AN: 152302 Hom.: 133 Cov.: 31 AF XY: 0.0213 AC XY: 1588 AN XY: 74470

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.00961

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00650 Hom.: 33

Bravo AF: 0.0248

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.1
Dann	Benign	0.80

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

Other links and lift over

dbSNP: rs11466334; hg19: chr19-41847737;