rs17636747

Positions:

• chr2-105261413-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001328646.3(TGFBRAP1):​c.2406+7859G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 152,152 control chromosomes in the GnomAD database, including 55 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 0.019 (55 hom., cov: 32)
• Consequence: TGFBRAP1 NM_001328646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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]

TGFBRAP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0188 (2866/152152) while in subpopulation NFE AF= 0.0279 (1896/68010). AF 95% confidence interval is 0.0268. There are 55 homozygotes in gnomad4. There are 1407 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2866 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBRAP1	NM_001328646.3	c.2406+7859G>A		intron_variant			NP_001315575.1
TGFBRAP1	XM_047446424.1	c.2406+7859G>A		intron_variant
		n.105261413C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2868 AN: 152034 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.00459

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0239

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

GnomAD4 genome AF: 0.0188 AC: 2866 AN: 152152 Hom.: 55 Cov.: 32 AF XY: 0.0189 AC XY: 1407 AN XY: 74396

Gnomad4 AFR AF: 0.00458

Gnomad4 AMR AF: 0.0184

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0102

Gnomad4 FIN AF: 0.0326

Gnomad4 NFE AF: 0.0279

Gnomad4 OTH AF: 0.0236

Alfa AF: 0.0250 Hom.: 28

Bravo AF: 0.0171

Asia WGS AF: 0.00433 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17636747; hg19: chr2-105877870;