chr1-91720237-AAAG-A

Variant names:

• chr1-91720237-AAAG-A
• rs565379527
• NM_003243.5:c.1076-10_1076-8delCTT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_003243.5(TGFBR3):​c.1076-10_1076-8delCTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,576,342 control chromosomes in the GnomAD database, including 5 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: TGFBR3 NM_003243.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.329
• Publications: 0 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 -6 ACMG points.

• BP6: Variant 1-91720237-AAAG-A is Benign according to our data. Variant chr1-91720237-AAAG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 547817.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 167 AD gene.

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.1076-10_1076-8delCTT		splice_region intron	N/A	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.1076-13_1076-11delCTT		intron	N/A	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.1076-13_1076-11delCTT		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.1076-10_1076-8delCTT		splice_region intron	N/A	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000525962.5	TSL:1	c.1076-10_1076-8delCTT		splice_region intron	N/A	ENSP00000436127.1	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.1076-13_1076-11delCTT		intron	N/A	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 167 AN: 152226 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000859 AC: 157 AN: 182668 AF XY: 0.000724

Gnomad AFR exome AF: 0.000362

Gnomad AMR exome AF: 0.00245

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.00143

GnomAD4 exome AF: 0.00119 AC: 1692 AN: 1423998 Hom.: 4 AF XY: 0.00111 AC XY: 782 AN XY: 705030

African (AFR) AF: 0.000184 AC: 6 AN: 32660

American (AMR) AF: 0.00199 AC: 77 AN: 38740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25448

East Asian (EAS) AF: 0.00 AC: 0 AN: 37910

South Asian (SAS) AF: 0.00 AC: 0 AN: 82546

European-Finnish (FIN) AF: 0.000118 AC: 6 AN: 50638

Middle Eastern (MID) AF: 0.000200 AC: 1 AN: 5000

European-Non Finnish (NFE) AF: 0.00141 AC: 1536 AN: 1092138

Other (OTH) AF: 0.00112 AC: 66 AN: 58918

GnomAD4 genome AF: 0.00110 AC: 167 AN: 152344 Hom.: 1 Cov.: 32 AF XY: 0.00109 AC XY: 81 AN XY: 74506

African (AFR) AF: 0.000457 AC: 19 AN: 41572

American (AMR) AF: 0.00301 AC: 46 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00141 AC: 96 AN: 68034

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.00105

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Connective tissue disorder (1)
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)
-	-	1	TGFBR3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs565379527; hg19: chr1-92185794;