1-91692890-A-G

Variant names:

• chr1-91692890-A-G
• rs2765887
• NM_003243.5:c.2437+2782T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003243.5(TGFBR3):​c.2437+2782T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,056 control chromosomes in the GnomAD database, including 11,487 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 0.38 (11487 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.552 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	NM_003243.5	MANE Select	c.2437+2782T>C		intron	N/A	NP_003234.2
	TGFBR3	NM_001195683.2		c.2434+2782T>C		intron	N/A	NP_001182612.1
	TGFBR3	NM_001195684.1		c.2434+2782T>C		intron	N/A	NP_001182613.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.2437+2782T>C		intron	N/A	ENSP00000212355.4
	TGFBR3	ENST00000525962.5	TSL:1	c.2437+2782T>C		intron	N/A	ENSP00000436127.1
	TGFBR3	ENST00000370399.6	TSL:1	c.2434+2782T>C		intron	N/A	ENSP00000359426.2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58385 AN: 151938 Hom.: 11480 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.384 AC: 58420 AN: 152056 Hom.: 11487 Cov.: 32 AF XY: 0.387 AC XY: 28796 AN XY: 74332

African (AFR) AF: 0.316 AC: 13081 AN: 41448

American (AMR) AF: 0.447 AC: 6830 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1793 AN: 3468

East Asian (EAS) AF: 0.294 AC: 1521 AN: 5172

South Asian (SAS) AF: 0.569 AC: 2746 AN: 4822

European-Finnish (FIN) AF: 0.359 AC: 3793 AN: 10556

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27348 AN: 67988

Other (OTH) AF: 0.412 AC: 870 AN: 2114

Alfa AF: 0.393 Hom.: 22825

Bravo AF: 0.381

Asia WGS AF: 0.417 AC: 1452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.9
DANN	Benign	0.68
PhyloP100		0.20
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: rs2765887; hg19: chr1-92158447;