rs1805112

Variant names:

• chr1-91720100-C-T
• rs1805112
• NM_003243.5:c.1206G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_003243.5(TGFBR3):​c.1206G>A​(p.Pro402Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,613,776 control chromosomes in the GnomAD database, including 138,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P402P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.39 (12158 hom., cov: 32)
  • Exomes 𝑓: 0.41 (126144 hom.)
• Consequence: TGFBR3 NM_003243.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0870
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 1-91720100-C-T is Benign according to our data. Variant chr1-91720100-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059704.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.087 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003243.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	NM_003243.5	MANE Select	c.1206G>A	p.Pro402Pro	synonymous	Exon 9 of 17	NP_003234.2
	TGFBR3	NM_001195683.2		c.1203G>A	p.Pro401Pro	synonymous	Exon 9 of 17	NP_001182612.1
	TGFBR3	NM_001195684.1		c.1203G>A	p.Pro401Pro	synonymous	Exon 10 of 18	NP_001182613.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.1206G>A	p.Pro402Pro	synonymous	Exon 9 of 17	ENSP00000212355.4
	TGFBR3	ENST00000525962.5	TSL:1	c.1206G>A	p.Pro402Pro	synonymous	Exon 8 of 16	ENSP00000436127.1
	TGFBR3	ENST00000370399.6	TSL:1	c.1203G>A	p.Pro401Pro	synonymous	Exon 10 of 18	ENSP00000359426.2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59534 AN: 151856 Hom.: 12157 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.397

GnomAD2 exomes AF: 0.414 AC: 103814 AN: 250966 AF XY: 0.420

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.271

Gnomad ASJ exome AF: 0.430

Gnomad EAS exome AF: 0.547

Gnomad FIN exome AF: 0.485

Gnomad NFE exome AF: 0.431

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.413 AC: 604454 AN: 1461802 Hom.: 126144 Cov.: 65 AF XY: 0.415 AC XY: 301899 AN XY: 727198

African (AFR) AF: 0.310 AC: 10390 AN: 33480

American (AMR) AF: 0.281 AC: 12565 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 11335 AN: 26136

East Asian (EAS) AF: 0.440 AC: 17475 AN: 39682

South Asian (SAS) AF: 0.430 AC: 37122 AN: 86256

European-Finnish (FIN) AF: 0.484 AC: 25862 AN: 53410

Middle Eastern (MID) AF: 0.399 AC: 2295 AN: 5754

European-Non Finnish (NFE) AF: 0.416 AC: 462569 AN: 1111970

Other (OTH) AF: 0.411 AC: 24841 AN: 60390

GnomAD4 genome AF: 0.392 AC: 59564 AN: 151974 Hom.: 12158 Cov.: 32 AF XY: 0.395 AC XY: 29370 AN XY: 74290

African (AFR) AF: 0.307 AC: 12741 AN: 41440

American (AMR) AF: 0.345 AC: 5274 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1483 AN: 3470

East Asian (EAS) AF: 0.507 AC: 2616 AN: 5158

South Asian (SAS) AF: 0.449 AC: 2164 AN: 4816

European-Finnish (FIN) AF: 0.484 AC: 5105 AN: 10556

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28745 AN: 67960

Other (OTH) AF: 0.395 AC: 832 AN: 2104

Alfa AF: 0.401 Hom.: 10026

Bravo AF: 0.375

Asia WGS AF: 0.474 AC: 1646 AN: 3478

EpiCase AF: 0.424

EpiControl AF: 0.424

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TGFBR3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	2.3
DANN	Benign	0.54
PhyloP100		0.087
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1805112; hg19: chr1-92185657; COSMIC: COSV53021846;