rs420549

Positions:

• chr9-99152591-G-C
• chr9-99152591-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004612.4(TGFBR1):​c.*3286G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 228,664 control chromosomes in the GnomAD database, including 3,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2071 hom., cov: 32)
  • Exomes 𝑓: 0.17 (1177 hom.)
• Consequence: TGFBR1 NM_004612.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.462

Genes affected

TGFBR1 (HGNC:11772): (transforming growth factor beta receptor 1) The protein encoded by this gene forms a heteromeric complex with type II TGF-beta receptors when bound to TGF-beta, transducing the TGF-beta signal from the cell surface to the cytoplasm. The encoded protein is a serine/threonine protein kinase. Mutations in this gene have been associated with Loeys-Dietz aortic aneurysm syndrome (LDAS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

TGFBR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-99152591-G-C is Benign according to our data. Variant chr9-99152591-G-C is described in ClinVar as [Benign]. Clinvar id is 364164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR1	NM_004612.4	c.*3286G>C		3_prime_UTR_variant	9/9	ENST00000374994.9	NP_004603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR1	ENST00000374994.9	c.*3286G>C		3_prime_UTR_variant	9/9	1	NM_004612.4	ENSP00000364133.4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24073 AN: 152046 Hom.: 2073 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0138

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.168 AC: 12877 AN: 76500 Hom.: 1177 Cov.: 0 AF XY: 0.170 AC XY: 5997 AN XY: 35374

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.183

Gnomad4 EAS exome AF: 0.0588

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.158 AC: 24079 AN: 152164 Hom.: 2071 Cov.: 32 AF XY: 0.152 AC XY: 11276 AN XY: 74394

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.161

Alfa AF: 0.183 Hom.: 348

Bravo AF: 0.155

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Loeys-Dietz syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Loeys-Dietz syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.65

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: rs420549; hg19: chr9-101914873;