Variant chr2-70456472-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000295400.11(TGFA):c.232G>A(p.Val78Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000572 in 1,608,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

TGFA
ENST00000295400.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058140486).

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TGFA	NM_003236.4 linkuse as main transcript	c.232G>A	p.Val78Ile	missense_variant	4/6	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2 linkuse as main transcript	c.250G>A	p.Val84Ile	missense_variant	4/6		NP_001295087.1
TGFA	NM_001308159.2 linkuse as main transcript	c.247G>A	p.Val83Ile	missense_variant	4/6		NP_001295088.1
TGFA	NM_001099691.3 linkuse as main transcript	c.229G>A	p.Val77Ile	missense_variant	4/6		NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11 linkuse as main transcript	c.232G>A	p.Val78Ile	missense_variant	4/6	1	NM_003236.4	ENSP00000295400	P4	P01135-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000838

AC:

AN:

238770

Hom.:

AF XY:

0.000101

AC XY:

AN XY:

128830

show subpopulations

Gnomad AFR exome

AF:

0.000466

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000564

Gnomad SAS exome

AF:

0.0000699

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000557

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000536

AC:

AN:

1455704

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

723404

show subpopulations

Gnomad4 AFR exome

AF:

0.000360

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000473

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000469

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.232G>A (p.V78I) alteration is located in exon 4 (coding exon 4) of the TGFA gene. This alteration results from a G to A substitution at nucleotide position 232, causing the valine (V) at amino acid position 78 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;.;.;.;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.79

T;T;T;T;T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.058

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;.;.;.;.;.

MutationTaster

Benign

0.88

D;D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.50

N;N;N;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.34

T;T;T;T;T;T

Sift4G

Benign

0.45

T;T;T;T;T;.

Polyphen

0.023

B;B;B;B;B;.

Vest4

0.12

MVP

0.13

MPC

0.17

ClinPred

0.011

GERP RS

2.8

Varity_R

0.11

gMVP

0.65

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over