1-91705151-A-G

Variant names:

• chr1-91705151-A-G
• rs284875
• NM_003243.5:c.2287+3512T>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.2287+3512T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 152,030 control chromosomes in the GnomAD database, including 64,987 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 0.92 (64987 hom., cov: 30)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.935 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	NM_003243.5	MANE Select	c.2287+3512T>C		intron	N/A	NP_003234.2
	TGFBR3	NM_001195683.2		c.2284+3512T>C		intron	N/A	NP_001182612.1
	TGFBR3	NM_001195684.1		c.2284+3512T>C		intron	N/A	NP_001182613.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.2287+3512T>C		intron	N/A	ENSP00000212355.4
	TGFBR3	ENST00000525962.5	TSL:1	c.2287+3512T>C		intron	N/A	ENSP00000436127.1
	TGFBR3	ENST00000370399.6	TSL:1	c.2284+3512T>C		intron	N/A	ENSP00000359426.2

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140340 AN: 151914 Hom.: 64934 Cov.: 30

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.924 AC: 140452 AN: 152030 Hom.: 64987 Cov.: 30 AF XY: 0.925 AC XY: 68730 AN XY: 74306

African (AFR) AF: 0.897 AC: 37157 AN: 41426

American (AMR) AF: 0.938 AC: 14342 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3137 AN: 3472

East Asian (EAS) AF: 0.777 AC: 4017 AN: 5170

South Asian (SAS) AF: 0.943 AC: 4540 AN: 4816

European-Finnish (FIN) AF: 0.969 AC: 10192 AN: 10514

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 63985 AN: 68022

Other (OTH) AF: 0.927 AC: 1961 AN: 2116

Alfa AF: 0.929 Hom.: 9699

Bravo AF: 0.921

Asia WGS AF: 0.874 AC: 3038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.66
PhyloP100		-0.24
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: rs284875; hg19: chr1-92170708;