rs6550004

Variant names:

• chr3-30608415-C-A
• rs6550004
• NM_003242.6:c.94+1438C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-30608415-C-A
• chr3-30608415-C-G
• chr3-30608415-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003242.6(TGFBR2):​c.94+1438C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 151,982 control chromosomes in the GnomAD database, including 40,060 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 0.71 (40060 hom., cov: 30)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290
• Publications: 11 publications found

Genes affected

TGFBR2 (HGNC:11773): (transforming growth factor beta receptor 2) The protein encoded by this gene is a transmembrane protein that has a protein kinase domain, forms a heterodimeric complex with TGF-beta receptor type-1, and binds TGF-beta. This receptor/ligand complex phosphorylates proteins, which then enter the nucleus and regulate the transcription of genes related to cell proliferation, cell cycle arrest, wound healing, immunosuppression, and tumorigenesis. Mutations in this gene have been associated with Marfan Syndrome, Loeys-Deitz Aortic Aneurysm Syndrome, and the development of various types of tumors. Alternatively spliced transcript variants encoding different isoforms have been characterized. [provided by RefSeq, Aug 2017]

TGFBR2 Gene-Disease associations (from GenCC):

• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Loeys-Dietz syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, G2P
• Loeys-Dietz syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.94+1438C>A		intron_variant	Intron 1 of 6	ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.94+1438C>A		intron_variant	Intron 1 of 6	1	NM_003242.6	ENSP00000295754.5

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107421 AN: 151864 Hom.: 40050 Cov.: 30

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.735

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.707 AC: 107471 AN: 151982 Hom.: 40060 Cov.: 30 AF XY: 0.711 AC XY: 52833 AN XY: 74270

African (AFR) AF: 0.439 AC: 18163 AN: 41364

American (AMR) AF: 0.813 AC: 12428 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2735 AN: 3472

East Asian (EAS) AF: 0.880 AC: 4543 AN: 5164

South Asian (SAS) AF: 0.764 AC: 3685 AN: 4824

European-Finnish (FIN) AF: 0.841 AC: 8891 AN: 10574

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54514 AN: 67984

Other (OTH) AF: 0.734 AC: 1551 AN: 2114

Alfa AF: 0.700 Hom.: 6855

Bravo AF: 0.695

Asia WGS AF: 0.783 AC: 2723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.31
PhyloP100		0.29
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: rs6550004; hg19: chr3-30649907;