chr19-41348181-C-T

Variant names:

• chr19-41348181-C-T
• rs2241716
• NM_000660.7:c.516+114G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 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]

TGFB1 Gene-Disease associations (from GenCC):

• Camurati-Engelmann disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Ambry Genetics, PanelApp Australia
• inflammatory bowel disease, immunodeficiency, and encephalopathy

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.516+114G>A		intron	N/A	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.516+114G>A		intron	N/A	ENSP00000221930.4	A0A499FJK2
	TGFB1	ENST00000597453.1	TSL:1	n.47+114G>A		intron	N/A
	TGFB1	ENST00000890114.1		c.516+114G>A		intron	N/A	ENSP00000560173.1

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

African (AFR) AF: 0.0732 AC: 1869 AN: 25540

American (AMR) AF: 0.0270 AC: 1183 AN: 43752

Ashkenazi Jewish (ASJ) AF: 0.00974 AC: 227 AN: 23298

East Asian (EAS) AF: 0.335 AC: 12411 AN: 37068

South Asian (SAS) AF: 0.0744 AC: 5809 AN: 78112

European-Finnish (FIN) AF: 0.0594 AC: 2419 AN: 40748

Middle Eastern (MID) AF: 0.0246 AC: 83 AN: 3376

European-Non Finnish (NFE) AF: 0.00250 AC: 1923 AN: 769034

Other (OTH) AF: 0.0360 AC: 1696 AN: 47118

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

African (AFR) AF: 0.0727 AC: 2995 AN: 41200

American (AMR) AF: 0.0314 AC: 477 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.00953 AC: 33 AN: 3462

East Asian (EAS) AF: 0.298 AC: 1532 AN: 5140

South Asian (SAS) AF: 0.100 AC: 481 AN: 4808

European-Finnish (FIN) AF: 0.0680 AC: 706 AN: 10378

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.00367 AC: 249 AN: 67930

Other (OTH) AF: 0.0468 AC: 98 AN: 2096

Alfa AF: 0.0202 Hom.: 394

Bravo AF: 0.0426

Asia WGS AF: 0.177 AC: 612 AN: 3478

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
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.72
PhyloP100		-0.45
Mutation Taster		=100/0	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: rs2241716; hg19: chr19-41854086;