2-105266144-C-T

Variant names:

• chr2-105266144-C-T
• rs2241796
• NM_004257.6:c.*1239G>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.*1239G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,178 control chromosomes in the GnomAD database, including 3,267 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 0.19 (3267 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TGFBRAP1 NM_004257.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 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.*1239G>A		3_prime_UTR	Exon 12 of 12	NP_004248.2
	TGFBRAP1	NM_001142621.3		c.*1239G>A		3_prime_UTR	Exon 12 of 12	NP_001136093.1	Q8WUH2
	TGFBRAP1	NM_001328646.3		c.2406+3128G>A		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.*1239G>A		3_prime_UTR	Exon 12 of 12	ENSP00000377027.2	Q8WUH2
	TGFBRAP1	ENST00000595531.5	TSL:1	c.*1239G>A		3_prime_UTR	Exon 11 of 11	ENSP00000471434.2	Q8WUH2
	TGFBRAP1	ENST00000911279.1		c.*1239G>A		3_prime_UTR	Exon 12 of 12	ENSP00000581338.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28188 AN: 152060 Hom.: 3267 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0661

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.181

GnomAD2 exomes AF: 0.143 AC: 2 AN: 14 AF XY: 0.250

Gnomad ASJ exome AF: 0.500

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.100

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.185 AC: 28209 AN: 152178 Hom.: 3267 Cov.: 33 AF XY: 0.189 AC XY: 14046 AN XY: 74394

African (AFR) AF: 0.259 AC: 10767 AN: 41514

American (AMR) AF: 0.197 AC: 3009 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3472

East Asian (EAS) AF: 0.513 AC: 2646 AN: 5160

South Asian (SAS) AF: 0.234 AC: 1127 AN: 4818

European-Finnish (FIN) AF: 0.131 AC: 1395 AN: 10616

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8324 AN: 67990

Other (OTH) AF: 0.188 AC: 397 AN: 2116

Alfa AF: 0.170 Hom.: 342

Bravo AF: 0.196

Asia WGS AF: 0.363 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		-0.87
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2241796;

hg19: chr2-105882601;