Variant chr2-70456428-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003236.4(TGFA):c.276T>C(p.Ala92Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,603,898 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 2 hom. )

Consequence

TGFA
NM_003236.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.96

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:

TGFA (HGNC:):

TGFA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-70456428-A-G is Benign according to our data. Variant chr2-70456428-A-G is described in ClinVar as [Benign]. Clinvar id is 746325.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.96 with no splicing effect.

BS2

High AC in GnomAd4 at 168 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFA	NM_003236.4 linkuse as main transcript	c.276T>C	p.Ala92Ala	synonymous_variant	4/6	ENST00000295400.11	NP_003227.1	P01135-1
TGFA	NM_001308158.2 linkuse as main transcript	c.294T>C	p.Ala98Ala	synonymous_variant	4/6		NP_001295087.1	P01135F8VNR3
TGFA	NM_001308159.2 linkuse as main transcript	c.291T>C	p.Ala97Ala	synonymous_variant	4/6		NP_001295088.1	P01135E7EPT6
TGFA	NM_001099691.3 linkuse as main transcript	c.273T>C	p.Ala91Ala	synonymous_variant	4/6		NP_001093161.1	P01135-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11 linkuse as main transcript	c.276T>C	p.Ala92Ala	synonymous_variant	4/6	1	NM_003236.4	ENSP00000295400.6		P01135-1

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

168

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00371

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

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:

0.0000735

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000250

AC:

AN:

231892

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

125258

show subpopulations

Gnomad AFR exome

AF:

0.00337

Gnomad AMR exome

AF:

0.000241

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000192

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000145

AC:

210

AN:

1451516

Hom.:

Cov.:

AF XY:

0.0000999

AC XY:

AN XY:

720956

show subpopulations

Gnomad4 AFR exome

AF:

0.00491

Gnomad4 AMR exome

AF:

0.000297

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000542

Gnomad4 OTH exome

AF:

0.000350

GnomAD4 genome

AF:

0.00110

AC:

168

AN:

152382

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00370

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000724

Hom.:

Bravo

AF:

0.00130

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.2

DANN

Benign

0.56

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