chr1-91900617-T-C

Variant names:

• chr1-91900617-T-C
• rs17576372
• ENST00000370399.6:c.-174-920A>G

Variant summary

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

The NM_001195684.1(TGFBR3):​c.-174-920A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,174 control chromosomes in the GnomAD database, including 9,441 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 0.33 (9441 hom., cov: 33)
• Consequence: TGFBR3 NM_001195684.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 6 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195684.1. 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_001195684.1		c.-174-920A>G		intron	N/A	NP_001182613.1	A0A0A8KWK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000370399.6	TSL:1	c.-174-920A>G		intron	N/A	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50056 AN: 152056 Hom.: 9438 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.329 AC: 50062 AN: 152174 Hom.: 9441 Cov.: 33 AF XY: 0.333 AC XY: 24801 AN XY: 74378

African (AFR) AF: 0.139 AC: 5790 AN: 41564

American (AMR) AF: 0.435 AC: 6642 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1492 AN: 3470

East Asian (EAS) AF: 0.211 AC: 1092 AN: 5174

South Asian (SAS) AF: 0.352 AC: 1699 AN: 4826

European-Finnish (FIN) AF: 0.453 AC: 4781 AN: 10558

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27312 AN: 67994

Other (OTH) AF: 0.339 AC: 717 AN: 2112

Alfa AF: 0.375 Hom.: 40410

Bravo AF: 0.321

Asia WGS AF: 0.326 AC: 1131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.1
DANN	Benign	0.94
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17576372; hg19: chr1-92366174;