1-91701384-C-T

Variant names:

• chr1-91701384-C-T
• rs284871
• NM_003243.5:c.2288-3254G>A

Variant summary

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

The NM_003243.5(TGFBR3):​c.2288-3254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 152,126 control chromosomes in the GnomAD database, including 66,541 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 0.93 (66541 hom., cov: 30)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.2288-3254G>A		intron_variant	Intron 14 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.2288-3254G>A		intron_variant	Intron 14 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142058 AN: 152008 Hom.: 66483 Cov.: 30

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.933

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

GnomAD4 genome AF: 0.935 AC: 142176 AN: 152126 Hom.: 66541 Cov.: 30 AF XY: 0.936 AC XY: 69555 AN XY: 74350

African (AFR) AF: 0.936 AC: 38867 AN: 41514

American (AMR) AF: 0.944 AC: 14438 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3136 AN: 3470

East Asian (EAS) AF: 0.767 AC: 3930 AN: 5124

South Asian (SAS) AF: 0.942 AC: 4537 AN: 4814

European-Finnish (FIN) AF: 0.969 AC: 10253 AN: 10578

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.940 AC: 63930 AN: 68020

Other (OTH) AF: 0.930 AC: 1964 AN: 2112

Alfa AF: 0.940 Hom.: 9570

Bravo AF: 0.933

Asia WGS AF: 0.872 AC: 3033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.68
PhyloP100		0.031
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: rs284871; hg19: chr1-92166941;