1-91689780-T-C

Variant names:

• chr1-91689780-T-C
• rs12082710
• NM_003243.5:c.2437+5892A>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.2437+5892A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 139,718 control chromosomes in the GnomAD database, including 9,768 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 (9768 hom., cov: 24)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.2437+5892A>G		intron_variant	Intron 16 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.2437+5892A>G		intron_variant	Intron 16 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.380 AC: 53128 AN: 139640 Hom.: 9766 Cov.: 24

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.380 AC: 53159 AN: 139718 Hom.: 9768 Cov.: 24 AF XY: 0.379 AC XY: 25318 AN XY: 66850

African (AFR) AF: 0.408 AC: 15352 AN: 37672

American (AMR) AF: 0.359 AC: 4586 AN: 12784

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1095 AN: 3410

East Asian (EAS) AF: 0.103 AC: 462 AN: 4490

South Asian (SAS) AF: 0.287 AC: 1272 AN: 4434

European-Finnish (FIN) AF: 0.400 AC: 3229 AN: 8078

Middle Eastern (MID) AF: 0.442 AC: 100 AN: 226

European-Non Finnish (NFE) AF: 0.395 AC: 25985 AN: 65860

Other (OTH) AF: 0.376 AC: 707 AN: 1880

Alfa AF: 0.367 Hom.: 33687

Bravo AF: 0.360

Asia WGS AF: 0.188 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.53
PhyloP100		-0.16
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: rs12082710; hg19: chr1-92155337; COSMIC: COSV53023281;