rs1030877

Positions:

• chr2-105294056-G-A

Variant summary

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

The NM_004257.6(TGFBRAP1):​c.1038+2300C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,002 control chromosomes in the GnomAD database, including 28,567 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 0.61 (28567 hom., cov: 32)
• Consequence: TGFBRAP1 NM_004257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBRAP1	NM_004257.6	c.1038+2300C>T		intron_variant		ENST00000393359.7	NP_004248.2
TGFBRAP1	NM_001142621.3	c.1038+2300C>T		intron_variant			NP_001136093.1
TGFBRAP1	NM_001426428.1	c.1038+2300C>T		intron_variant			NP_001413357.1
TGFBRAP1	NM_001328646.3	c.1038+2300C>T		intron_variant			NP_001315575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBRAP1	ENST00000393359.7	c.1038+2300C>T		intron_variant		1	NM_004257.6	ENSP00000377027.2
TGFBRAP1	ENST00000595531.5	c.1038+2300C>T		intron_variant		1		ENSP00000471434.2

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92358 AN: 151884 Hom.: 28544 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.608 AC: 92443 AN: 152002 Hom.: 28567 Cov.: 32 AF XY: 0.601 AC XY: 44628 AN XY: 74294

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.590

Alfa AF: 0.634 Hom.: 19127

Bravo AF: 0.607

Asia WGS AF: 0.434 AC: 1506 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.079
DANN	Benign	0.45

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: rs1030877; hg19: chr2-105910513;