rs10874915

Positions:

• chr1-91736878-C-G
• chr1-91736878-C-T

Variant summary

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

The NM_003243.5(TGFBR3):​c.385-1919G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,196 control chromosomes in the GnomAD database, including 48,181 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 0.79 (48181 hom., cov: 33)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.385-1919G>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.385-1919G>C		intron_variant		1	NM_003243.5	ENSP00000212355	P3

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119451 AN: 152080 Hom.: 48159 Cov.: 33

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.785 AC: 119517 AN: 152196 Hom.: 48181 Cov.: 33 AF XY: 0.781 AC XY: 58105 AN XY: 74400

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.889

Gnomad4 OTH AF: 0.818

Alfa AF: 0.776 Hom.: 2539

Bravo AF: 0.781

Asia WGS AF: 0.715 AC: 2489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.67

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: rs10874915; hg19: chr1-92202435;