NM_003243.5:c.-114+10751T>C

Variant names:

• chr1-91875127-A-G
• rs1192524
• NM_003243.5:c.-114+10751T>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.-114+10751T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,028 control chromosomes in the GnomAD database, including 41,228 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 0.73 (41228 hom., cov: 31)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.-114+10751T>C		intron_variant	Intron 1 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.-114+10751T>C		intron_variant	Intron 1 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111270 AN: 151910 Hom.: 41168 Cov.: 31

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.733 AC: 111387 AN: 152028 Hom.: 41228 Cov.: 31 AF XY: 0.728 AC XY: 54093 AN XY: 74292

African (AFR) AF: 0.845 AC: 35046 AN: 41472

American (AMR) AF: 0.717 AC: 10948 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2438 AN: 3464

East Asian (EAS) AF: 0.796 AC: 4096 AN: 5148

South Asian (SAS) AF: 0.723 AC: 3473 AN: 4802

European-Finnish (FIN) AF: 0.593 AC: 6267 AN: 10572

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46764 AN: 67990

Other (OTH) AF: 0.735 AC: 1549 AN: 2108

Alfa AF: 0.691 Hom.: 19422

Bravo AF: 0.747

Asia WGS AF: 0.709 AC: 2469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.1
DANN	Benign	0.51
PhyloP100		-0.17
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: rs1192524; hg19: chr1-92340684;