2-105281283-T-G

Variant names:

• chr2-105281283-T-G
• rs1020064
• NM_004257.6:c.1122-560A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004257.6(TGFBRAP1):​c.1122-560A>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 152,132 control chromosomes in the GnomAD database, including 47,323 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 (47323 hom., cov: 32)
• Consequence: TGFBRAP1 NM_004257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBRAP1	NM_004257.6	c.1122-560A>C		intron_variant	Intron 5 of 11	ENST00000393359.7	NP_004248.2
TGFBRAP1	NM_001142621.3	c.1122-560A>C		intron_variant	Intron 5 of 11		NP_001136093.1
TGFBRAP1	NM_001328646.3	c.1122-560A>C		intron_variant	Intron 5 of 11		NP_001315575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBRAP1	ENST00000393359.7	c.1122-560A>C		intron_variant	Intron 5 of 11	1	NM_004257.6	ENSP00000377027.2
TGFBRAP1	ENST00000595531.5	c.1122-560A>C		intron_variant	Intron 4 of 10	1		ENSP00000471434.2

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119702 AN: 152014 Hom.: 47276 Cov.: 32

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.788 AC: 119809 AN: 152132 Hom.: 47323 Cov.: 32 AF XY: 0.784 AC XY: 58311 AN XY: 74376

African (AFR) AF: 0.822 AC: 34132 AN: 41504

American (AMR) AF: 0.822 AC: 12566 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2446 AN: 3466

East Asian (EAS) AF: 0.793 AC: 4095 AN: 5164

South Asian (SAS) AF: 0.759 AC: 3651 AN: 4812

European-Finnish (FIN) AF: 0.729 AC: 7714 AN: 10576

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52734 AN: 68002

Other (OTH) AF: 0.782 AC: 1654 AN: 2114

Alfa AF: 0.776 Hom.: 158346

Bravo AF: 0.797

Asia WGS AF: 0.804 AC: 2795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.42
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1020064; hg19: chr2-105897740;