rs1473486

Positions:

• chr1-91776019-T-C

Variant summary

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

The NM_003243.5(TGFBR3):​c.247-17269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,096 control chromosomes in the GnomAD database, including 19,454 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 0.50 (19454 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.247-17269A>G		intron_variant		ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.247-17269A>G		intron_variant		1	NM_003243.5	ENSP00000212355	P3

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75854 AN: 151978 Hom.: 19423 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.499 AC: 75936 AN: 152096 Hom.: 19454 Cov.: 32 AF XY: 0.497 AC XY: 36934 AN XY: 74378

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.495

Alfa AF: 0.479 Hom.: 6842

Bravo AF: 0.504

Asia WGS AF: 0.451 AC: 1572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.077
DANN	Benign	0.63

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: rs1473486; hg19: chr1-92241576;