chr1-91738246-T-C

Variant names:

• chr1-91738246-T-C
• rs2087299
• NM_003243.5:c.385-3287A>G

Variant summary

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

The NM_003243.5(TGFBR3):​c.385-3287A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,158 control chromosomes in the GnomAD database, including 17,469 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 0.46 (17469 hom., cov: 33)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.385-3287A>G		intron_variant	Intron 4 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.385-3287A>G		intron_variant	Intron 4 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70709 AN: 152040 Hom.: 17450 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.465 AC: 70746 AN: 152158 Hom.: 17469 Cov.: 33 AF XY: 0.466 AC XY: 34663 AN XY: 74390

African (AFR) AF: 0.288 AC: 11973 AN: 41512

American (AMR) AF: 0.527 AC: 8064 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2510 AN: 5170

South Asian (SAS) AF: 0.514 AC: 2481 AN: 4826

European-Finnish (FIN) AF: 0.534 AC: 5656 AN: 10590

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36851 AN: 67984

Other (OTH) AF: 0.498 AC: 1052 AN: 2114

Alfa AF: 0.492 Hom.: 7728

Bravo AF: 0.459

Asia WGS AF: 0.469 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.84
PhyloP100		-1.0
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: rs2087299; hg19: chr1-92203803;