rs7550034

chr1-91899019-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000370399.6(TGFBR3):c.-114+618T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,084 control chromosomes in the GnomAD database, including 15,058 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 0.44 (15058 hom., cov: 32)
• Consequence: TGFBR3 ENST00000370399.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195

Genes affected

TGFBR3 (HGNC:11774): (transforming growth factor beta receptor 3) This locus encodes the transforming growth factor (TGF)-beta type III receptor. The encoded receptor is a membrane proteoglycan that often functions as a co-receptor with other TGF-beta receptor superfamily members. Ectodomain shedding produces soluble TGFBR3, which may inhibit TGFB signaling. Decreased expression of this receptor has been observed in various cancers. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_001195684.1	c.-114+618T>C		intron_variant
TGFBR3	XM_047429247.1	c.-114+618T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000370399.6	c.-114+618T>C		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66680 AN: 151966 Hom.: 15054 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.439 AC: 66701 AN: 152084 Hom.: 15058 Cov.: 32 AF XY: 0.440 AC XY: 32707 AN XY: 74332

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.444

Alfa AF: 0.469 Hom.: 9445

Bravo AF: 0.436

Asia WGS AF: 0.377 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.5
Dann	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7550034; hg19: chr1-92364576;