chr3-30643636-T-G

Position:

• chr3-30643636-T-G

Variant summary

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

The ENST00000295754.10(TGFBR2):​c.95-1111T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 152,304 control chromosomes in the GnomAD database, including 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 0.038 (122 hom., cov: 32)
• Consequence: TGFBR2 ENST00000295754.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.038 (5782/152304) while in subpopulation NFE AF= 0.0453 (3084/68020). AF 95% confidence interval is 0.044. There are 122 homozygotes in gnomad4. There are 2699 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5782 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.95-1111T>G		intron_variant		ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.95-1111T>G		intron_variant		1	NM_003242.6	ENSP00000295754	P1
TGFBR2	ENST00000359013.4	c.170-1111T>G		intron_variant		1		ENSP00000351905
TGFBR2	ENST00000672866.1	n.1691-1111T>G		intron_variant, non_coding_transcript_variant
TGFBR2	ENST00000673250.1	n.219-1111T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5781 AN: 152186 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0394

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.0445

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0380 AC: 5782 AN: 152304 Hom.: 122 Cov.: 32 AF XY: 0.0362 AC XY: 2699 AN XY: 74478

Gnomad4 AFR AF: 0.0340

Gnomad4 AMR AF: 0.0394

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.00482

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.0345

Gnomad4 NFE AF: 0.0453

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0412 Hom.: 25

Bravo AF: 0.0385

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.81
DANN	Benign	0.46

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: rs17025862; hg19: chr3-30685128;