NM_004257.6:c.1665+507G>A

Variant names:

• chr2-105275053-C-T
• rs2576737
• NM_004257.6:c.1665+507G>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.1665+507G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,954 control chromosomes in the GnomAD database, including 26,104 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 0.58 (26104 hom., cov: 31)
• Consequence: TGFBRAP1 NM_004257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 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.1665+507G>A		intron	N/A	NP_004248.2
	TGFBRAP1	NM_001142621.3		c.1665+507G>A		intron	N/A	NP_001136093.1
	TGFBRAP1	NM_001328646.3		c.1665+507G>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.1665+507G>A		intron	N/A	ENSP00000377027.2
	TGFBRAP1	ENST00000595531.5	TSL:1	c.1665+507G>A		intron	N/A	ENSP00000471434.2
	TGFBRAP1	ENST00000911279.1		c.1665+507G>A		intron	N/A	ENSP00000581338.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87739 AN: 151836 Hom.: 26086 Cov.: 31

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.578 AC: 87813 AN: 151954 Hom.: 26104 Cov.: 31 AF XY: 0.571 AC XY: 42433 AN XY: 74262

African (AFR) AF: 0.479 AC: 19831 AN: 41422

American (AMR) AF: 0.618 AC: 9440 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2010 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1428 AN: 5138

South Asian (SAS) AF: 0.523 AC: 2521 AN: 4818

European-Finnish (FIN) AF: 0.597 AC: 6306 AN: 10558

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44346 AN: 67956

Other (OTH) AF: 0.580 AC: 1222 AN: 2108

Alfa AF: 0.598 Hom.: 3992

Bravo AF: 0.573

Asia WGS AF: 0.435 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.34
PhyloP100		-0.67
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: rs2576737; hg19: chr2-105891510;