rs2038931

Variant names:

• chr1-91708858-G-A
• rs2038931
• NM_003243.5:c.2167-75C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-91708858-G-A
• chr1-91708858-G-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.2167-75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,582,730 control chromosomes in the GnomAD database, including 15,541 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 0.16 (2285 hom., cov: 32)
  • Exomes 𝑓: 0.12 (13256 hom.)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973
• Publications: 9 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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.2167-75C>T		intron_variant	Intron 13 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.2167-75C>T		intron_variant	Intron 13 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24014 AN: 152040 Hom.: 2271 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.123 AC: 175423 AN: 1430572 Hom.: 13256 AF XY: 0.121 AC XY: 85852 AN XY: 709942

African (AFR) AF: 0.215 AC: 7018 AN: 32602

American (AMR) AF: 0.192 AC: 7812 AN: 40754

Ashkenazi Jewish (ASJ) AF: 0.0451 AC: 1154 AN: 25602

East Asian (EAS) AF: 0.418 AC: 15871 AN: 37966

South Asian (SAS) AF: 0.0971 AC: 8046 AN: 82878

European-Finnish (FIN) AF: 0.196 AC: 10017 AN: 51040

Middle Eastern (MID) AF: 0.0716 AC: 309 AN: 4318

European-Non Finnish (NFE) AF: 0.107 AC: 117297 AN: 1096256

Other (OTH) AF: 0.134 AC: 7899 AN: 59156

GnomAD4 genome AF: 0.158 AC: 24057 AN: 152158 Hom.: 2285 Cov.: 32 AF XY: 0.163 AC XY: 12161 AN XY: 74392

African (AFR) AF: 0.218 AC: 9025 AN: 41486

American (AMR) AF: 0.168 AC: 2571 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 149 AN: 3470

East Asian (EAS) AF: 0.391 AC: 2026 AN: 5176

South Asian (SAS) AF: 0.101 AC: 489 AN: 4828

European-Finnish (FIN) AF: 0.207 AC: 2191 AN: 10588

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7176 AN: 68002

Other (OTH) AF: 0.146 AC: 308 AN: 2108

Alfa AF: 0.119 Hom.: 1583

Bravo AF: 0.159

Asia WGS AF: 0.261 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.73
PhyloP100		0.97
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: rs2038931; hg19: chr1-92174415; COSMIC: COSV53028691;