rs11466259

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003236.4(TGFA):c.325G>A(p.Val109Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,572,908 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 34 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 28 hom. )

Consequence

TGFA
NM_003236.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.49

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

tooth agenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TGFA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004414737).

BP6

Variant 2-70456379-C-T is Benign according to our data. Variant chr2-70456379-C-T is described in ClinVar as [Benign]. Clinvar id is 709603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.011 (1678/152332) while in subpopulation AFR AF = 0.0373 (1549/41568). AF 95% confidence interval is 0.0357. There are 34 homozygotes in GnomAd4. There are 770 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1678 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4 link	c.325G>A	p.Val109Met	missense_variant	Exon 4 of 6	ENST00000295400.11	NP_003227.1	P01135-1
TGFA	NM_001308158.2 link	c.343G>A	p.Val115Met	missense_variant	Exon 4 of 6		NP_001295087.1	P01135F8VNR3
TGFA	NM_001308159.2 link	c.340G>A	p.Val114Met	missense_variant	Exon 4 of 6		NP_001295088.1	P01135E7EPT6
TGFA	NM_001099691.3 link	c.322G>A	p.Val108Met	missense_variant	Exon 4 of 6		NP_001093161.1	P01135-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11 link	c.325G>A	p.Val109Met	missense_variant	Exon 4 of 6	1	NM_003236.4	ENSP00000295400.6		P01135-1

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1675

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0373

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

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:

0.000235

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00260

AC:

485

AN:

186612

AF XY:

0.00195

show subpopulations

Gnomad AFR exome

AF:

0.0377

Gnomad AMR exome

AF:

0.00166

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000372

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000127

Gnomad OTH exome

AF:

0.000409

GnomAD4 exome

AF:

0.00112

AC:

1587

AN:

1420576

Hom.:

Cov.:

AF XY:

0.000952

AC XY:

669

AN XY:

702820

show subpopulations

African (AFR)

AF:

0.0388

AC:

1258

AN:

32390

American (AMR)

AF:

0.00215

AC:

AN:

39086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25348

East Asian (EAS)

AF:

0.000108

AC:

AN:

37006

South Asian (SAS)

AF:

0.0000994

AC:

AN:

80514

European-Finnish (FIN)

AF:

0.0000197

AC:

AN:

50800

Middle Eastern (MID)

AF:

0.00140

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000743

AC:

AN:

1090840

Other (OTH)

AF:

0.00243

AC:

143

AN:

58868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

187

280

374

467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0110

AC:

1678

AN:

152332

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

770

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0373

AC:

1549

AN:

41568

American (AMR)

AF:

0.00601

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68030

Other (OTH)

AF:

0.00992

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

164

245

327

409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00371

Hom.:

Bravo

AF:

0.0130

ESP6500AA

AF:

0.0329

AC:

145

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00255

AC:

308

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

D;.;.;.;.;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

MetaRNN

Benign

0.0044

T;T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

2.9

M;.;.;.;.;.

PhyloP100

3.5

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.0

N;N;N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.11

T;T;T;T;T;D

Sift4G

Uncertain

0.0060

D;D;D;D;D;.

Polyphen

1.0

D;D;D;D;D;.

Vest4

0.28

MVP

0.44

MPC

0.79

ClinPred

0.053

GERP RS

4.6

Varity_R

0.15

gMVP

0.70

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs11466259

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over