rs1030878

Positions:

• chr2-105294141-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004257.6(TGFBRAP1):​c.1038+2215A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,150 control chromosomes in the GnomAD database, including 47,436 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 0.79 (47436 hom., cov: 32)
• Consequence: TGFBRAP1 NM_004257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

Genes affected

TGFBRAP1 (HGNC:16836): (transforming growth factor beta receptor associated protein 1) This gene encodes a protein that binds to transforming growth factor-beta (TGF-beta) receptors and plays a role in TGF-beta signaling. The encoded protein acts as a chaprone in signaling downstream of TGF-beta. It is involved in signal-dependent association with SMAD4. The protein is also a component of mammalian CORVET, a multisubunit tethering protein complex that is involved in fusion of early endosomes. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBRAP1	NM_004257.6	c.1038+2215A>C		intron_variant		ENST00000393359.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBRAP1	ENST00000393359.7	c.1038+2215A>C		intron_variant		1	NM_004257.6	P1
TGFBRAP1	ENST00000595531.5	c.1038+2215A>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119849 AN: 152032 Hom.: 47388 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.788 AC: 119958 AN: 152150 Hom.: 47436 Cov.: 32 AF XY: 0.785 AC XY: 58396 AN XY: 74378

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.775

Alfa AF: 0.783 Hom.: 5831

Bravo AF: 0.798

Asia WGS AF: 0.803 AC: 2791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.9
DANN	Benign	0.73

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: rs1030878; hg19: chr2-105910598;