1-91870527-T-G

Position:

• chr1-91870527-T-G

Variant summary

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

The NM_003243.5(TGFBR3):​c.-113-8883A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,106 control chromosomes in the GnomAD database, including 30,513 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 0.63 (30513 hom., cov: 33)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100

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]

TGFBR3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.-113-8883A>C		intron_variant		ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.-113-8883A>C		intron_variant		1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95853 AN: 151988 Hom.: 30500 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.631 AC: 95907 AN: 152106 Hom.: 30513 Cov.: 33 AF XY: 0.624 AC XY: 46410 AN XY: 74342

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.633

Alfa AF: 0.639 Hom.: 5056

Bravo AF: 0.633

Asia WGS AF: 0.473 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.62

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: rs6656018; hg19: chr1-92336084;