1-91735070-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003243.5. 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_003243.5	MANE Select	c.385-111A>G		intron	N/A	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.385-111A>G		intron	N/A	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.385-111A>G		intron	N/A	NP_001182613.1	A0A0A8KWK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.385-111A>G		intron	N/A	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000525962.5	TSL:1	c.385-111A>G		intron	N/A	ENSP00000436127.1	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.385-111A>G		intron	N/A	ENSP00000359426.2	Q03167-2

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

African (AFR) AF: 0.677 AC: 18115 AN: 26752

American (AMR) AF: 0.981 AC: 41697 AN: 42498

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 23672 AN: 23862

East Asian (EAS) AF: 0.997 AC: 37571 AN: 37676

South Asian (SAS) AF: 0.999 AC: 77973 AN: 78034

European-Finnish (FIN) AF: 1.00 AC: 42547 AN: 42548

Middle Eastern (MID) AF: 0.978 AC: 5012 AN: 5124

European-Non Finnish (NFE) AF: 0.999 AC: 829663 AN: 830610

Other (OTH) AF: 0.977 AC: 48821 AN: 49988

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

African (AFR) AF: 0.678 AC: 28137 AN: 41474

American (AMR) AF: 0.962 AC: 14724 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3443 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5161 AN: 5182

South Asian (SAS) AF: 0.998 AC: 4818 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10621 AN: 10622

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67925 AN: 68034

Other (OTH) AF: 0.933 AC: 1970 AN: 2112

Alfa AF: 0.863 Hom.: 22056

Bravo AF: 0.894

Asia WGS AF: 0.968 AC: 3363 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.34
PhyloP100		0.019
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: rs10874913; hg19: chr1-92200627;