1-91892629-G-C

Variant names:

• chr1-91892629-G-C
• rs6680463
• ENST00000370399.6:c.-114+7008C>G

Variant summary

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

The ENST00000370399.6(TGFBR3):​c.-114+7008C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,940 control chromosomes in the GnomAD database, including 18,520 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 0.49 (18520 hom., cov: 31)
• Consequence: TGFBR3 ENST00000370399.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_001195684.1	c.-114+7008C>G		intron_variant	Intron 2 of 17		NP_001182613.1
TGFBR3	XM_047429247.1	c.-114+7008C>G		intron_variant	Intron 2 of 17		XP_047285203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000370399.6	c.-114+7008C>G		intron_variant	Intron 2 of 17	1		ENSP00000359426.2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74966 AN: 151822 Hom.: 18502 Cov.: 31

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.494 AC: 75028 AN: 151940 Hom.: 18520 Cov.: 31 AF XY: 0.491 AC XY: 36431 AN XY: 74268

African (AFR) AF: 0.491 AC: 20337 AN: 41422

American (AMR) AF: 0.498 AC: 7602 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1502 AN: 3468

East Asian (EAS) AF: 0.385 AC: 1987 AN: 5160

South Asian (SAS) AF: 0.439 AC: 2112 AN: 4814

European-Finnish (FIN) AF: 0.467 AC: 4927 AN: 10544

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34963 AN: 67958

Other (OTH) AF: 0.480 AC: 1011 AN: 2108

Alfa AF: 0.498 Hom.: 2323

Bravo AF: 0.496

Asia WGS AF: 0.403 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.66
PhyloP100		0.56
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: rs6680463; hg19: chr1-92358186;