rs7550034

Variant names:

• chr1-91899019-A-G
• rs7550034
• ENST00000370399.6:c.-114+618T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000370399.6(TGFBR3):​c.-114+618T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,084 control chromosomes in the GnomAD database, including 15,058 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 0.44 (15058 hom., cov: 32)
• Consequence: TGFBR3 ENST00000370399.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370399.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	NM_001195684.1		c.-114+618T>C		intron	N/A	NP_001182613.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000370399.6	TSL:1	c.-114+618T>C		intron	N/A	ENSP00000359426.2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66680 AN: 151966 Hom.: 15054 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.439 AC: 66701 AN: 152084 Hom.: 15058 Cov.: 32 AF XY: 0.440 AC XY: 32707 AN XY: 74332

African (AFR) AF: 0.352 AC: 14586 AN: 41490

American (AMR) AF: 0.514 AC: 7856 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1780 AN: 3470

East Asian (EAS) AF: 0.213 AC: 1103 AN: 5172

South Asian (SAS) AF: 0.439 AC: 2114 AN: 4818

European-Finnish (FIN) AF: 0.486 AC: 5134 AN: 10560

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32586 AN: 67988

Other (OTH) AF: 0.444 AC: 937 AN: 2108

Alfa AF: 0.455 Hom.: 13884

Bravo AF: 0.436

Asia WGS AF: 0.377 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.70
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7550034; hg19: chr1-92364576;