rs11466531

Variant names:

• chr3-30692346-C-G
• rs11466531
• NM_003242.6:c.*747C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-30692346-C-G
• chr3-30692346-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003242.6(TGFBR2):​c.*747C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 230,126 control chromosomes in the GnomAD database, including 1,414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1232 hom., cov: 32)
  • Exomes 𝑓: 0.057 (182 hom.)
• Consequence: TGFBR2 NM_003242.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.182
• Publications: 13 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, Unknown Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Loeys-Dietz syndrome 2

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-30692346-C-G is Benign according to our data. Variant chr3-30692346-C-G is described in ClinVar as Benign. ClinVar VariationId is 344681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003242.6. 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
	TGFBR2	NM_003242.6	MANE Select	c.*747C>G		3_prime_UTR	Exon 7 of 7	NP_003233.4
	TGFBR2	NM_001407126.1		c.*747C>G		3_prime_UTR	Exon 9 of 9	NP_001394055.1
	TGFBR2	NM_001407127.1		c.*747C>G		3_prime_UTR	Exon 8 of 8	NP_001394056.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR2	ENST00000295754.10	TSL:1 MANE Select	c.*747C>G		3_prime_UTR	Exon 7 of 7	ENSP00000295754.5	P37173-1
	TGFBR2	ENST00000359013.4	TSL:1	c.*747C>G		3_prime_UTR	Exon 8 of 8	ENSP00000351905.4	P37173-2
	TGFBR2	ENST00000941789.1		c.*747C>G		3_prime_UTR	Exon 7 of 7	ENSP00000611848.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15525 AN: 152046 Hom.: 1224 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.0955

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0845

GnomAD4 exome AF: 0.0571 AC: 4452 AN: 77962 Hom.: 182 Cov.: 0 AF XY: 0.0552 AC XY: 1977 AN XY: 35832

African (AFR) AF: 0.194 AC: 716 AN: 3686

American (AMR) AF: 0.155 AC: 369 AN: 2374

Ashkenazi Jewish (ASJ) AF: 0.0659 AC: 326 AN: 4944

East Asian (EAS) AF: 0.0148 AC: 165 AN: 11136

South Asian (SAS) AF: 0.0855 AC: 58 AN: 678

European-Finnish (FIN) AF: 0.0795 AC: 7 AN: 88

Middle Eastern (MID) AF: 0.0519 AC: 25 AN: 482

European-Non Finnish (NFE) AF: 0.0474 AC: 2279 AN: 48088

Other (OTH) AF: 0.0782 AC: 507 AN: 6486

GnomAD4 genome AF: 0.102 AC: 15564 AN: 152164 Hom.: 1232 Cov.: 32 AF XY: 0.104 AC XY: 7740 AN XY: 74398

African (AFR) AF: 0.202 AC: 8391 AN: 41472

American (AMR) AF: 0.146 AC: 2233 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 247 AN: 3470

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5180

South Asian (SAS) AF: 0.0950 AC: 458 AN: 4822

European-Finnish (FIN) AF: 0.0626 AC: 664 AN: 10610

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0477 AC: 3246 AN: 68010

Other (OTH) AF: 0.0836 AC: 176 AN: 2106

Alfa AF: 0.0148 Hom.: 5

Bravo AF: 0.112

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)
-	-	1	Loeys-Dietz syndrome 2 (1)
-	-	1	Marfan syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.39
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11466531; hg19: chr3-30733838;