dbSNP rs1058213: TGFA:c.*528C>T (chr2-70450331-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003236.4(TGFA):c.*528C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,630 control chromosomes in the GnomAD database, including 4,528 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 ( 4519 hom., cov: 32)

Exomes 𝑓: 0.15 ( 9 hom. )

Consequence

TGFA
NM_003236.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.772

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003236.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TGFA	NM_003236.4	MANE Select	c.*528C>T	3_prime_UTR	Exon 6 of 6	NP_003227.1
TGFA	NM_001308158.2		c.*528C>T	3_prime_UTR	Exon 6 of 6	NP_001295087.1
TGFA	NM_001308159.2		c.*528C>T	3_prime_UTR	Exon 6 of 6	NP_001295088.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TGFA	ENST00000295400.11	TSL:1 MANE Select	c.*528C>T	3_prime_UTR	Exon 6 of 6	ENSP00000295400.6
TGFA	ENST00000418333.6	TSL:1	c.*528C>T	3_prime_UTR	Exon 6 of 6	ENSP00000404099.2
TGFA	ENST00000445399.5	TSL:1	c.*19-710C>T	intron	N/A	ENSP00000387493.1

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35570

AN:

151912

Hom.:

4511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.156

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:

0.226

GnomAD4 exome

AF:

0.150

AC:

AN:

600

Hom.:

Cov.:

AF XY:

0.135

AC XY:

AN XY:

318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.100

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

AN:

East Asian (EAS)

AF:

0.182

AC:

AN:

South Asian (SAS)

AF:

0.0556

AC:

AN:

European-Finnish (FIN)

AF:

0.292

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.157

AC:

AN:

408

Other (OTH)

AF:

0.192

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.234

AC:

35588

AN:

152030

Hom.:

4519

Cov.:

AF XY:

0.234

AC XY:

17382

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.162

AC:

6736

AN:

41476

American (AMR)

AF:

0.155

AC:

2376

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

717

AN:

3470

East Asian (EAS)

AF:

0.298

AC:

1538

AN:

5164

South Asian (SAS)

AF:

0.229

AC:

1102

AN:

4812

European-Finnish (FIN)

AF:

0.309

AC:

3259

AN:

10546

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.280

AC:

19024

AN:

67964

Other (OTH)

AF:

0.234

AC:

493

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1362

2723

4085

5446

6808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.248

Hom.:

1093

Bravo

AF:

0.220

Asia WGS

AF:

0.287

AC:

999

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.7

(source)

DANN

Benign

0.73

PhyloP100

0.77

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over