rs2129972

Variant names:

• chr1-91839693-C-T
• rs2129972
• NM_003243.5:c.61+21778G>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.61+21778G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,992 control chromosomes in the GnomAD database, including 1,717 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 0.13 (1717 hom., cov: 31)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.61+21778G>A		intron_variant	Intron 2 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.61+21778G>A		intron_variant	Intron 2 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20406 AN: 151872 Hom.: 1713 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0893

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.134 AC: 20426 AN: 151992 Hom.: 1717 Cov.: 31 AF XY: 0.135 AC XY: 10030 AN XY: 74276

African (AFR) AF: 0.192 AC: 7977 AN: 41450

American (AMR) AF: 0.117 AC: 1780 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 457 AN: 3468

East Asian (EAS) AF: 0.383 AC: 1972 AN: 5150

South Asian (SAS) AF: 0.108 AC: 522 AN: 4816

European-Finnish (FIN) AF: 0.120 AC: 1270 AN: 10544

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0893 AC: 6068 AN: 67974

Other (OTH) AF: 0.127 AC: 268 AN: 2114

Alfa AF: 0.101 Hom.: 949

Bravo AF: 0.139

Asia WGS AF: 0.224 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.30
PhyloP100		-0.35
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: rs2129972; hg19: chr1-92305250;