1-91736878-C-G

Variant names:

• chr1-91736878-C-G
• rs10874915
• NM_003243.5:c.385-1919G>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.385-1919G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,196 control chromosomes in the GnomAD database, including 48,181 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 0.79 (48181 hom., cov: 33)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003243.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	NM_003243.5	MANE Select	c.385-1919G>C		intron	N/A	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.385-1919G>C		intron	N/A	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.385-1919G>C		intron	N/A	NP_001182613.1	A0A0A8KWK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.385-1919G>C		intron	N/A	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000525962.5	TSL:1	c.385-1919G>C		intron	N/A	ENSP00000436127.1	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.385-1919G>C		intron	N/A	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119451 AN: 152080 Hom.: 48159 Cov.: 33

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.785 AC: 119517 AN: 152196 Hom.: 48181 Cov.: 33 AF XY: 0.781 AC XY: 58105 AN XY: 74400

African (AFR) AF: 0.588 AC: 24410 AN: 41500

American (AMR) AF: 0.830 AC: 12700 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2869 AN: 3468

East Asian (EAS) AF: 0.745 AC: 3854 AN: 5172

South Asian (SAS) AF: 0.751 AC: 3619 AN: 4818

European-Finnish (FIN) AF: 0.832 AC: 8827 AN: 10604

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60480 AN: 68016

Other (OTH) AF: 0.818 AC: 1726 AN: 2110

Alfa AF: 0.776 Hom.: 2539

Bravo AF: 0.781

Asia WGS AF: 0.715 AC: 2489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.67
PhyloP100		0.031
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: rs10874915; hg19: chr1-92202435;