2-105290023-C-G

Variant names:

• chr2-105290023-C-G
• rs2679895
• NM_004257.6:c.1039-5625G>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.1039-5625G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,196 control chromosomes in the GnomAD database, including 47,556 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 (47556 hom., cov: 33)
• Consequence: TGFBRAP1 NM_004257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004257.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBRAP1	NM_004257.6	MANE Select	c.1039-5625G>C		intron	N/A	NP_004248.2
	TGFBRAP1	NM_001142621.3		c.1039-5625G>C		intron	N/A	NP_001136093.1
	TGFBRAP1	NM_001328646.3		c.1039-5625G>C		intron	N/A	NP_001315575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBRAP1	ENST00000393359.7	TSL:1 MANE Select	c.1039-5625G>C		intron	N/A	ENSP00000377027.2
	TGFBRAP1	ENST00000595531.5	TSL:1	c.1039-5625G>C		intron	N/A	ENSP00000471434.2
	TGFBRAP1	ENST00000911279.1		c.1039-5625G>C		intron	N/A	ENSP00000581338.1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 120018 AN: 152076 Hom.: 47504 Cov.: 33

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.789 AC: 120131 AN: 152196 Hom.: 47556 Cov.: 33 AF XY: 0.786 AC XY: 58458 AN XY: 74394

African (AFR) AF: 0.829 AC: 34451 AN: 41544

American (AMR) AF: 0.822 AC: 12566 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2445 AN: 3470

East Asian (EAS) AF: 0.793 AC: 4110 AN: 5184

South Asian (SAS) AF: 0.758 AC: 3663 AN: 4830

European-Finnish (FIN) AF: 0.730 AC: 7722 AN: 10576

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52713 AN: 67986

Other (OTH) AF: 0.780 AC: 1644 AN: 2108

Alfa AF: 0.781 Hom.: 5438

Bravo AF: 0.799

Asia WGS AF: 0.806 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.64
PhyloP100		0.15
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: rs2679895; hg19: chr2-105906480;