1-91728765-C-A

Position:

• chr1-91728765-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003243.5(TGFBR3):​c.738-959G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,940 control chromosomes in the GnomAD database, including 24,529 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 0.55 (24529 hom., cov: 31)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5	c.738-959G>T		intron_variant		ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9	c.738-959G>T		intron_variant		1	NM_003243.5	P3

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83213 AN: 151820 Hom.: 24515 Cov.: 31

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.548 AC: 83259 AN: 151940 Hom.: 24529 Cov.: 31 AF XY: 0.548 AC XY: 40716 AN XY: 74252

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.577

Alfa AF: 0.627 Hom.: 39525

Bravo AF: 0.540

Asia WGS AF: 0.633 AC: 2203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs11165354; hg19: chr1-92194322;