chr3-30641447-G-C

Position:

• chr3-30641447-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003242.6(TGFBR2):​c.95-3300G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,808 control chromosomes in the GnomAD database, including 7,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.29 (7460 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.414

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-30641447-G-C is Benign according to our data. Variant chr3-30641447-G-C is described in ClinVar as [Benign]. Clinvar id is 225780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.95-3300G>C		intron_variant		ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.95-3300G>C		intron_variant		1	NM_003242.6	ENSP00000295754.5
TGFBR2	ENST00000359013.4	c.170-3300G>C		intron_variant		1		ENSP00000351905.4
TGFBR2	ENST00000672866.1	n.1691-3300G>C		intron_variant
TGFBR2	ENST00000673250.1	n.219-3300G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44161 AN: 151688 Hom.: 7470 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.291 AC: 44152 AN: 151808 Hom.: 7460 Cov.: 31 AF XY: 0.295 AC XY: 21880 AN XY: 74150

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.297

Alfa AF: 0.211 Hom.: 573

Bravo AF: 0.278

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 27, 2025

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.68

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: rs12493607; hg19: chr3-30682939;