1-91697786-T-C

Variant names:

• chr1-91697786-T-C
• rs2765889
• NM_003243.5:c.2329+303A>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.2329+303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,124 control chromosomes in the GnomAD database, including 42,293 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 0.74 (42293 hom., cov: 33)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.2329+303A>G		intron_variant	Intron 15 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.2329+303A>G		intron_variant	Intron 15 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112690 AN: 152004 Hom.: 42257 Cov.: 33

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.741 AC: 112771 AN: 152124 Hom.: 42293 Cov.: 33 AF XY: 0.737 AC XY: 54774 AN XY: 74362

African (AFR) AF: 0.793 AC: 32902 AN: 41484

American (AMR) AF: 0.730 AC: 11160 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2661 AN: 3464

East Asian (EAS) AF: 0.375 AC: 1944 AN: 5182

South Asian (SAS) AF: 0.828 AC: 3994 AN: 4822

European-Finnish (FIN) AF: 0.648 AC: 6858 AN: 10586

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.747 AC: 50795 AN: 67984

Other (OTH) AF: 0.736 AC: 1553 AN: 2110

Alfa AF: 0.748 Hom.: 5225

Bravo AF: 0.747

Asia WGS AF: 0.599 AC: 2085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.12
DANN	Benign	0.62
PhyloP100		-1.4
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: rs2765889; hg19: chr1-92163343;