chr1-91749071-T-C

Variant names:

• chr1-91749071-T-C
• rs284170
• NM_003243.5:c.384+9542A>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.384+9542A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,120 control chromosomes in the GnomAD database, including 57,009 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 0.86 (57009 hom., cov: 31)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.384+9542A>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.384+9542A>G		intron_variant	Intron 4 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131357 AN: 152002 Hom.: 56949 Cov.: 31

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.864 AC: 131476 AN: 152120 Hom.: 57009 Cov.: 31 AF XY: 0.863 AC XY: 64146 AN XY: 74342

African (AFR) AF: 0.930 AC: 38570 AN: 41492

American (AMR) AF: 0.854 AC: 13046 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2766 AN: 3472

East Asian (EAS) AF: 0.799 AC: 4131 AN: 5172

South Asian (SAS) AF: 0.756 AC: 3636 AN: 4810

European-Finnish (FIN) AF: 0.857 AC: 9070 AN: 10578

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57483 AN: 68006

Other (OTH) AF: 0.850 AC: 1799 AN: 2116

Alfa AF: 0.852 Hom.: 163343

Bravo AF: 0.867

Asia WGS AF: 0.766 AC: 2666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.58
PhyloP100		0.091
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs284170; hg19: chr1-92214628;