rs284185

Positions:

• chr1-91768263-T-A
• chr1-91768263-T-G

Variant summary

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

The NM_003243.5(TGFBR3):​c.247-9513A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,258 control chromosomes in the GnomAD database, including 23,061 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 0.55 (23061 hom., cov: 29)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645

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]

TGFBR3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.247-9513A>T		intron_variant		ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.247-9513A>T		intron_variant		1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82387 AN: 151142 Hom.: 23033 Cov.: 29

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.545 AC: 82461 AN: 151258 Hom.: 23061 Cov.: 29 AF XY: 0.545 AC XY: 40226 AN XY: 73826

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.529

Alfa AF: 0.418 Hom.: 1081

Bravo AF: 0.535

Asia WGS AF: 0.353 AC: 1231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.79

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: rs284185; hg19: chr1-92233820;