chr1-91692890-A-G

Position:

• chr1-91692890-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.2437+2782T>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.2437+2782T>C		intron_variant		1	NM_003243.5	ENSP00000212355	P3

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

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.412

Alfa AF: 0.393 Hom.: 13400

Bravo AF: 0.381

Asia WGS AF: 0.417 AC: 1452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.9
DANN	Benign	0.68

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: rs2765887; hg19: chr1-92158447;