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. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Likely benign (no stars).

• 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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-30608415-C-A is Benign according to our data. Variant chr3-30608415-C-A is described in Lovd as [Likely_benign].
• 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
TGFBR2	ENST00000359013.4	c.94+1438C>A		intron_variant	Intron 1 of 7	1		ENSP00000351905.4

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

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.788

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.841

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.734

Alfa AF: 0.708 Hom.: 6780

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

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: rs6550004; hg19: chr3-30649907;