1-91735070-T-C

Variant names:

• chr1-91735070-T-C
• rs10874913
• NM_003243.5:c.385-111A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003243.5(TGFBR3):​c.385-111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 1,289,324 control chromosomes in the GnomAD database, including 622,122 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 0.91 (64084 hom., cov: 32)
  • Exomes 𝑓: 0.99 (558038 hom.)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.385-111A>G		intron_variant	Intron 4 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.385-111A>G		intron_variant	Intron 4 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.907 AC: 137921 AN: 152114 Hom.: 64060 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.933

GnomAD4 exome AF: 0.989 AC: 1125071 AN: 1137092 Hom.: 558038 AF XY: 0.991 AC XY: 574644 AN XY: 579984

Gnomad4 AFR exome AF: 0.677

Gnomad4 AMR exome AF: 0.981

Gnomad4 ASJ exome AF: 0.992

Gnomad4 EAS exome AF: 0.997

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.977

GnomAD4 genome AF: 0.906 AC: 137992 AN: 152232 Hom.: 64084 Cov.: 32 AF XY: 0.909 AC XY: 67702 AN XY: 74466

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.962

Gnomad4 ASJ AF: 0.992

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.998

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.933

Alfa AF: 0.941 Hom.: 8362

Bravo AF: 0.894

Asia WGS AF: 0.968 AC: 3363 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs10874913; hg19: chr1-92200627;