1-91897245-C-T

Variant names:

• chr1-91897245-C-T
• rs12566180
• ENST00000370399.6:c.-114+2392G>A

Variant summary

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

The ENST00000370399.6(TGFBR3):​c.-114+2392G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,020 control chromosomes in the GnomAD database, including 16,141 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 0.46 (16141 hom., cov: 32)
• Consequence: TGFBR3 ENST00000370399.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_001195684.1	c.-114+2392G>A		intron_variant	Intron 2 of 17		NP_001182613.1
TGFBR3	XM_047429247.1	c.-114+2392G>A		intron_variant	Intron 2 of 17		XP_047285203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000370399.6	c.-114+2392G>A		intron_variant	Intron 2 of 17	1		ENSP00000359426.2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69341 AN: 151902 Hom.: 16140 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.456 AC: 69376 AN: 152020 Hom.: 16141 Cov.: 32 AF XY: 0.454 AC XY: 33747 AN XY: 74286

African (AFR) AF: 0.362 AC: 15027 AN: 41462

American (AMR) AF: 0.482 AC: 7355 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1502 AN: 3468

East Asian (EAS) AF: 0.384 AC: 1980 AN: 5158

South Asian (SAS) AF: 0.437 AC: 2107 AN: 4820

European-Finnish (FIN) AF: 0.469 AC: 4940 AN: 10538

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34921 AN: 67988

Other (OTH) AF: 0.453 AC: 957 AN: 2112

Alfa AF: 0.467 Hom.: 10215

Bravo AF: 0.454

Asia WGS AF: 0.392 AC: 1365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.091
DANN	Benign	0.64
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12566180; hg19: chr1-92362802;