1-91816523-T-G

Variant names:

• chr1-91816523-T-G
• rs2129975
• NM_003243.5:c.62-19052A>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.62-19052A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,014 control chromosomes in the GnomAD database, including 21,791 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 0.53 (21791 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.62-19052A>C		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.62-19052A>C		intron_variant	Intron 2 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81065 AN: 151896 Hom.: 21771 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.534 AC: 81129 AN: 152014 Hom.: 21791 Cov.: 32 AF XY: 0.532 AC XY: 39524 AN XY: 74298

African (AFR) AF: 0.524 AC: 21708 AN: 41460

American (AMR) AF: 0.542 AC: 8272 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1702 AN: 3472

East Asian (EAS) AF: 0.401 AC: 2074 AN: 5166

South Asian (SAS) AF: 0.591 AC: 2850 AN: 4822

European-Finnish (FIN) AF: 0.488 AC: 5148 AN: 10554

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37651 AN: 67956

Other (OTH) AF: 0.541 AC: 1141 AN: 2110

Alfa AF: 0.553 Hom.: 12009

Bravo AF: 0.536

Asia WGS AF: 0.494 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.31
DANN	Benign	0.80
PhyloP100		-1.2
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: rs2129975; hg19: chr1-92282080;