19-41348181-C-T

Variant names:

• chr19-41348181-C-T
• rs2241716
• NM_000660.7:c.516+114G>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.516+114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,219,444 control chromosomes in the GnomAD database, including 3,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (439 hom., cov: 30)
  • Exomes 𝑓: 0.026 (2728 hom.)
• Consequence: TGFB1 NM_000660.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.448

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 19-41348181-C-T is Benign according to our data. Variant chr19-41348181-C-T is described in ClinVar as [Benign]. Clinvar id is 1288925.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFB1	NM_000660.7	c.516+114G>A		intron_variant	Intron 2 of 6	ENST00000221930.6	NP_000651.3
TGFB1	XM_011527242.3	c.516+114G>A		intron_variant	Intron 2 of 6		XP_011525544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFB1	ENST00000221930.6	c.516+114G>A		intron_variant	Intron 2 of 6	1	NM_000660.7	ENSP00000221930.4
TGFB1	ENST00000597453.1	n.47+114G>A		intron_variant	Intron 1 of 2	1
TGFB1	ENST00000600196.2	c.516+114G>A		intron_variant	Intron 2 of 5	5		ENSP00000504008.1
TGFB1	ENST00000677934.1	c.516+114G>A		intron_variant	Intron 2 of 4			ENSP00000504769.1

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6569 AN: 151300 Hom.: 437 Cov.: 30

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.00953

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.00367

Gnomad OTH AF: 0.0462

GnomAD4 exome AF: 0.0259 AC: 27620 AN: 1068046 Hom.: 2728 AF XY: 0.0271 AC XY: 14873 AN XY: 548108

Gnomad4 AFR exome AF: 0.0732

Gnomad4 AMR exome AF: 0.0270

Gnomad4 ASJ exome AF: 0.00974

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.0744

Gnomad4 FIN exome AF: 0.0594

Gnomad4 NFE exome AF: 0.00250

Gnomad4 OTH exome AF: 0.0360

GnomAD4 genome AF: 0.0435 AC: 6581 AN: 151398 Hom.: 439 Cov.: 30 AF XY: 0.0496 AC XY: 3664 AN XY: 73882

Gnomad4 AFR AF: 0.0727

Gnomad4 AMR AF: 0.0314

Gnomad4 ASJ AF: 0.00953

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.00367

Gnomad4 OTH AF: 0.0468

Alfa AF: 0.0268 Hom.: 22

Bravo AF: 0.0426

Asia WGS AF: 0.177 AC: 612 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.72

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: rs2241716; hg19: chr19-41854086;