chr1-91845317-G-A

Variant names:

• chr1-91845317-G-A
• rs6686126
• NM_003243.5:c.61+16154C>T

Variant summary

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

The NM_003243.5(TGFBR3):​c.61+16154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0934 in 152,204 control chromosomes in the GnomAD database, including 905 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 0.093 (905 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.61+16154C>T		intron_variant	Intron 2 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.61+16154C>T		intron_variant	Intron 2 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.0934 AC: 14205 AN: 152086 Hom.: 904 Cov.: 32

Gnomad AFR AF: 0.0885

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0856

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.0867

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

GnomAD4 genome AF: 0.0934 AC: 14215 AN: 152204 Hom.: 905 Cov.: 32 AF XY: 0.0971 AC XY: 7229 AN XY: 74412

African (AFR) AF: 0.0884 AC: 3674 AN: 41542

American (AMR) AF: 0.0857 AC: 1310 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1810 AN: 5164

South Asian (SAS) AF: 0.152 AC: 734 AN: 4822

European-Finnish (FIN) AF: 0.109 AC: 1154 AN: 10588

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0749 AC: 5094 AN: 68020

Other (OTH) AF: 0.0877 AC: 185 AN: 2110

Alfa AF: 0.0784 Hom.: 106

Bravo AF: 0.0910

Asia WGS AF: 0.239 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.10
DANN	Benign	0.62
PhyloP100		-2.0
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: rs6686126; hg19: chr1-92310874;