Variant 2-70450862-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003236.4(TGFA):c.480C>T(p.Val160=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,607,768 control chromosomes in the GnomAD database, including 57,977 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 0.23 ( 4518 hom., cov: 32)

Exomes 𝑓: 0.27 ( 53459 hom. )

Consequence

TGFA
NM_003236.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02

Variant links:

Genes affected

TGFA (HGNC:11765): (transforming growth factor alpha) This gene encodes a growth factor that is a ligand for the epidermal growth factor receptor, which activates a signaling pathway for cell proliferation, differentiation and development. This protein may act as either a transmembrane-bound ligand or a soluble ligand. This gene has been associated with many types of cancers, and it may also be involved in some cases of cleft lip/palate. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

TGFA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=2.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TGFA	NM_003236.4 linkuse as main transcript	c.480C>T	p.Val160=	synonymous_variant	6/6	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2 linkuse as main transcript	c.498C>T	p.Val166=	synonymous_variant	6/6		NP_001295087.1
TGFA	NM_001308159.2 linkuse as main transcript	c.495C>T	p.Val165=	synonymous_variant	6/6		NP_001295088.1
TGFA	NM_001099691.3 linkuse as main transcript	c.477C>T	p.Val159=	synonymous_variant	6/6		NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11 linkuse as main transcript	c.480C>T	p.Val160=	synonymous_variant	6/6	1	NM_003236.4	ENSP00000295400	P4	P01135-1

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35557

AN:

151954

Hom.:

4510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.225

GnomAD3 exomes

AF:

0.240

AC:

58120

AN:

242456

Hom.:

7581

AF XY:

0.244

AC XY:

31952

AN XY:

130752

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.299

Gnomad SAS exome

AF:

0.223

Gnomad FIN exome

AF:

0.310

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.242

GnomAD4 exome

AF:

0.267

AC:

388789

AN:

1455696

Hom.:

53459

Cov.:

AF XY:

0.266

AC XY:

192735

AN XY:

723506

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.212

Gnomad4 EAS exome

AF:

0.280

Gnomad4 SAS exome

AF:

0.222

Gnomad4 FIN exome

AF:

0.310

Gnomad4 NFE exome

AF:

0.280

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.234

AC:

35575

AN:

152072

Hom.:

4518

Cov.:

AF XY:

0.234

AC XY:

17378

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.162

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.207

Gnomad4 EAS

AF:

0.298

Gnomad4 SAS

AF:

0.229

Gnomad4 FIN

AF:

0.309

Gnomad4 NFE

AF:

0.280

Gnomad4 OTH

AF:

0.234

Alfa

AF:

0.251

Hom.:

5414

Bravo

AF:

0.220

Asia WGS

AF:

0.287

AC:

999

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.4

DANN

Benign

0.66

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over