dbSNP rs3771527: TGFA:c.*3409T>A (chr2-70447450-A-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_003236.4(TGFA):c.*3409T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,680 control chromosomes in the GnomAD database, including 1,971 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 0.15 ( 1964 hom., cov: 33)

Exomes 𝑓: 0.17 ( 7 hom. )

Consequence

TGFA
NM_003236.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4 link	c.*3409T>A	3_prime_UTR_variant	Exon 6 of 6	ENST00000295400.11	NP_003227.1	P01135-1
TGFA	NM_001308158.2 link	c.*3409T>A	3_prime_UTR_variant	Exon 6 of 6		NP_001295087.1	P01135F8VNR3
TGFA	NM_001308159.2 link	c.*3409T>A	3_prime_UTR_variant	Exon 6 of 6		NP_001295088.1	P01135E7EPT6
TGFA	NM_001099691.3 link	c.*3409T>A	3_prime_UTR_variant	Exon 6 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.*3409T>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_003236.4	ENSP00000295400.6		P01135-1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22407

AN:

152138

Hom.:

1961

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.140

GnomAD4 exome

AF:

0.171

AC:

AN:

426

Hom.:

Cov.:

AF XY:

0.171

AC XY:

AN XY:

258

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.171

AC:

AN:

420

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.147

AC:

22422

AN:

152254

Hom.:

1964

Cov.:

AF XY:

0.153

AC XY:

11373

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.141

AC:

5855

AN:

41558

American (AMR)

AF:

0.269

AC:

4122

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

363

AN:

3472

East Asian (EAS)

AF:

0.173

AC:

897

AN:

5190

South Asian (SAS)

AF:

0.169

AC:

814

AN:

4816

European-Finnish (FIN)

AF:

0.189

AC:

1997

AN:

10590

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7963

AN:

68010

Other (OTH)

AF:

0.139

AC:

294

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1003

2006

3008

4011

5014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.109

Hom.:

166

Bravo

AF:

0.155

Asia WGS

AF:

0.170

AC:

590

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over