1-91728105-A-G

Variant names:

• chr1-91728105-A-G
• rs6696224
• NM_003243.5:c.738-299T>C

Variant summary

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

The NM_003243.5(TGFBR3):​c.738-299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,212 control chromosomes in the GnomAD database, including 1,986 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 0.15 (1986 hom., cov: 33)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 7 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.738-299T>C		intron_variant	Intron 6 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.738-299T>C		intron_variant	Intron 6 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22197 AN: 152094 Hom.: 1980 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.146 AC: 22214 AN: 152212 Hom.: 1986 Cov.: 33 AF XY: 0.152 AC XY: 11336 AN XY: 74406

African (AFR) AF: 0.157 AC: 6514 AN: 41534

American (AMR) AF: 0.159 AC: 2439 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3468

East Asian (EAS) AF: 0.446 AC: 2306 AN: 5172

South Asian (SAS) AF: 0.102 AC: 493 AN: 4826

European-Finnish (FIN) AF: 0.208 AC: 2203 AN: 10582

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7681 AN: 68012

Other (OTH) AF: 0.139 AC: 293 AN: 2110

Alfa AF: 0.141 Hom.: 648

Bravo AF: 0.147

Asia WGS AF: 0.260 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.4
DANN	Benign	0.68
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs6696224; hg19: chr1-92193662;