chr1-91683720-C-G

Variant names:

• chr1-91683720-C-G
• rs1131243
• ENST00000532540.5:n.*2522G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000532540.5(TGFBR3):​n.*2522G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,261,744 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 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 0.000089 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TGFBR3 ENST00000532540.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.*19G>C		3_prime_UTR_variant	Exon 17 of 17	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.*19G>C		3_prime_UTR_variant	Exon 17 of 17	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.0000895 AC: 13 AN: 145198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000997

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000684

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000232

Gnomad SAS AF: 0.000495

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000606

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000182 AC: 23 AN: 1261744 Hom.: 0 Cov.: 31 AF XY: 0.0000241 AC XY: 15 AN XY: 622120

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27626

American (AMR) AF: 0.00 AC: 0 AN: 32490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20566

East Asian (EAS) AF: 0.0000798 AC: 2 AN: 25078

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77764

European-Finnish (FIN) AF: 0.0000761 AC: 2 AN: 26270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3624

European-Non Finnish (NFE) AF: 0.0000170 AC: 17 AN: 998802

Other (OTH) AF: 0.0000202 AC: 1 AN: 49524

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000043), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000895 AC: 13 AN: 145330 Hom.: 0 Cov.: 32 AF XY: 0.0000847 AC XY: 6 AN XY: 70826

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000995 AC: 4 AN: 40218

American (AMR) AF: 0.0000683 AC: 1 AN: 14636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3370

East Asian (EAS) AF: 0.000232 AC: 1 AN: 4316

South Asian (SAS) AF: 0.000493 AC: 2 AN: 4054

European-Finnish (FIN) AF: 0.000106 AC: 1 AN: 9474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000606 AC: 4 AN: 66050

Other (OTH) AF: 0.00 AC: 0 AN: 2058

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.3
DANN	Benign	0.65
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism

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: rs1131243; hg19: chr1-92149277;