1-91776629-C-T

Variant names:

• chr1-91776629-C-T
• rs10874940
• NM_003243.5:c.247-17879G>A

Variant summary

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

The NM_003243.5(TGFBR3):​c.247-17879G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,130 control chromosomes in the GnomAD database, including 1,691 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 0.13 (1691 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.247-17879G>A		intron_variant	Intron 3 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.247-17879G>A		intron_variant	Intron 3 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20321 AN: 152012 Hom.: 1689 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0974

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0923

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.134 AC: 20341 AN: 152130 Hom.: 1691 Cov.: 32 AF XY: 0.134 AC XY: 9992 AN XY: 74358

African (AFR) AF: 0.219 AC: 9085 AN: 41484

American (AMR) AF: 0.0972 AC: 1487 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0583 AC: 202 AN: 3466

East Asian (EAS) AF: 0.248 AC: 1280 AN: 5160

South Asian (SAS) AF: 0.145 AC: 699 AN: 4818

European-Finnish (FIN) AF: 0.0937 AC: 992 AN: 10588

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0923 AC: 6275 AN: 68004

Other (OTH) AF: 0.126 AC: 267 AN: 2112

Alfa AF: 0.121 Hom.: 208

Bravo AF: 0.136

Asia WGS AF: 0.209 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.39
DANN	Benign	0.65
PhyloP100		-0.76
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: rs10874940; hg19: chr1-92242186;