NM_004257.6:c.1039-818G>A

Variant names:

• chr2-105285216-C-T
• rs3792048
• NM_004257.6:c.1039-818G>A

Variant summary

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

The NM_004257.6(TGFBRAP1):​c.1039-818G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 152,266 control chromosomes in the GnomAD database, including 1,029 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 0.095 (1029 hom., cov: 33)
• Consequence: TGFBRAP1 NM_004257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBRAP1	NM_004257.6	c.1039-818G>A		intron_variant	Intron 4 of 11	ENST00000393359.7	NP_004248.2
TGFBRAP1	NM_001142621.3	c.1039-818G>A		intron_variant	Intron 4 of 11		NP_001136093.1
TGFBRAP1	NM_001328646.3	c.1039-818G>A		intron_variant	Intron 4 of 11		NP_001315575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBRAP1	ENST00000393359.7	c.1039-818G>A		intron_variant	Intron 4 of 11	1	NM_004257.6	ENSP00000377027.2
TGFBRAP1	ENST00000595531.5	c.1039-818G>A		intron_variant	Intron 3 of 10	1		ENSP00000471434.2

Frequencies

GnomAD3 genomes AF: 0.0950 AC: 14461 AN: 152148 Hom.: 1030 Cov.: 33

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0914

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0790

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.0950 AC: 14465 AN: 152266 Hom.: 1029 Cov.: 33 AF XY: 0.0999 AC XY: 7436 AN XY: 74468

African (AFR) AF: 0.0610 AC: 2536 AN: 41564

American (AMR) AF: 0.157 AC: 2405 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 225 AN: 3468

East Asian (EAS) AF: 0.377 AC: 1942 AN: 5156

South Asian (SAS) AF: 0.148 AC: 714 AN: 4830

European-Finnish (FIN) AF: 0.0914 AC: 970 AN: 10616

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0789 AC: 5369 AN: 68014

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.0990 Hom.: 669

Bravo AF: 0.101

Asia WGS AF: 0.269 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.66
PhyloP100		-1.0
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: rs3792048; hg19: chr2-105901673;