1-91816523-T-G

Position:

• chr1-91816523-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.62-19052A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,014 control chromosomes in the GnomAD database, including 21,791 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 0.53 (21791 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5	c.62-19052A>C		intron_variant		ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9	c.62-19052A>C		intron_variant		1	NM_003243.5	P3

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81065 AN: 151896 Hom.: 21771 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.534 AC: 81129 AN: 152014 Hom.: 21791 Cov.: 32 AF XY: 0.532 AC XY: 39524 AN XY: 74298

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.541

Alfa AF: 0.553 Hom.: 10718

Bravo AF: 0.536

Asia WGS AF: 0.494 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.31
DANN	Benign	0.80

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: rs2129975; hg19: chr1-92282080;