1-91743109-T-C

Variant names:

• chr1-91743109-T-C
• rs4658112
• NM_003243.5:c.385-8150A>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.385-8150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 151,988 control chromosomes in the GnomAD database, including 31,235 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 0.64 (31235 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.385-8150A>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.385-8150A>G		intron_variant	Intron 4 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97035 AN: 151870 Hom.: 31203 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.639 AC: 97118 AN: 151988 Hom.: 31235 Cov.: 32 AF XY: 0.645 AC XY: 47904 AN XY: 74312

African (AFR) AF: 0.562 AC: 23263 AN: 41414

American (AMR) AF: 0.678 AC: 10357 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2176 AN: 3468

East Asian (EAS) AF: 0.741 AC: 3831 AN: 5170

South Asian (SAS) AF: 0.741 AC: 3570 AN: 4820

European-Finnish (FIN) AF: 0.705 AC: 7443 AN: 10556

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44348 AN: 67970

Other (OTH) AF: 0.649 AC: 1364 AN: 2102

Alfa AF: 0.590 Hom.: 2936

Bravo AF: 0.631

Asia WGS AF: 0.740 AC: 2574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		-0.38
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: rs4658112; hg19: chr1-92208666;