rs284176

Positions:

• chr1-91758419-A-G
• chr1-91758419-A-T

Variant summary

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

The NM_003243.5(TGFBR3):​c.384+194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,016 control chromosomes in the GnomAD database, including 35,078 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 0.68 (35078 hom., cov: 31)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.384+194T>C		intron_variant		ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.384+194T>C		intron_variant		1	NM_003243.5	ENSP00000212355	P3

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102989 AN: 151898 Hom.: 35044 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.678 AC: 103072 AN: 152016 Hom.: 35078 Cov.: 31 AF XY: 0.681 AC XY: 50623 AN XY: 74306

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.674

Alfa AF: 0.675 Hom.: 46281

Bravo AF: 0.674

Asia WGS AF: 0.601 AC: 2090 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.24

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: rs284176; hg19: chr1-92223976; COSMIC: COSV53030166;