1-91683720-C-A

Variant names:

• chr1-91683720-C-A
• rs1131243
• ENST00000532540.5:n.*2522G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000532540.5(TGFBR3):​n.*2522G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,261,762 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: TGFBR3 ENST00000532540.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.*19G>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.*19G>T		3_prime_UTR_variant	Exon 17 of 17	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1261762 Hom.: 0 Cov.: 31 AF XY: 0.00000161 AC XY: 1 AN XY: 622128

African (AFR) AF: 0.00 AC: 0 AN: 27628

American (AMR) AF: 0.00 AC: 0 AN: 32490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20566

East Asian (EAS) AF: 0.00 AC: 0 AN: 25080

South Asian (SAS) AF: 0.00 AC: 0 AN: 77764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3626

European-Non Finnish (NFE) AF: 0.00000200 AC: 2 AN: 998814

Other (OTH) AF: 0.00 AC: 0 AN: 49524

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	2.8
DANN	Benign	0.84
PhyloP100		-0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1131243; hg19: chr1-92149277;