NM_003242.6:c.455-111A>G

Variant names:

• chr3-30671527-A-G
• rs17026161
• NM_003242.6:c.455-111A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003242.6(TGFBR2):​c.455-111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,124,162 control chromosomes in the GnomAD database, including 3 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 0.00098 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (3 hom.)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423

Genes affected

TGFBR2 (HGNC:11773): (transforming growth factor beta receptor 2) The protein encoded by this gene is a transmembrane protein that has a protein kinase domain, forms a heterodimeric complex with TGF-beta receptor type-1, and binds TGF-beta. This receptor/ligand complex phosphorylates proteins, which then enter the nucleus and regulate the transcription of genes related to cell proliferation, cell cycle arrest, wound healing, immunosuppression, and tumorigenesis. Mutations in this gene have been associated with Marfan Syndrome, Loeys-Deitz Aortic Aneurysm Syndrome, and the development of various types of tumors. Alternatively spliced transcript variants encoding different isoforms have been characterized. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000985 (150/152338) while in subpopulation NFE AF= 0.0015 (102/68036). AF 95% confidence interval is 0.00126. There are 0 homozygotes in gnomad4. There are 68 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 150 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.455-111A>G		intron_variant	Intron 3 of 6	ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.455-111A>G		intron_variant	Intron 3 of 6	1	NM_003242.6	ENSP00000295754.5
TGFBR2	ENST00000359013.4	c.530-111A>G		intron_variant	Intron 4 of 7	1		ENSP00000351905.4
TGFBR2	ENST00000672866.1	n.2051-111A>G		intron_variant	Intron 3 of 6

Frequencies

GnomAD3 genomes AF: 0.000985 AC: 150 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.000955

GnomAD4 exome AF: 0.00115 AC: 1117 AN: 971824 Hom.: 3 AF XY: 0.00120 AC XY: 598 AN XY: 498700

Gnomad4 AFR exome AF: 0.000207

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.0000272

Gnomad4 SAS exome AF: 0.00159

Gnomad4 FIN exome AF: 0.000347

Gnomad4 NFE exome AF: 0.00124

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.000985 AC: 150 AN: 152338 Hom.: 0 Cov.: 33 AF XY: 0.000913 AC XY: 68 AN XY: 74494

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00150

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00120 Hom.: 0

Bravo AF: 0.00103

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.9
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: rs17026161; hg19: chr3-30713019;