rs1058213

Variant names:

• chr2-70450331-G-A
• rs1058213
• NM_003236.4:c.*528C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.772
• Publications: 9 publications found

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

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4	c.*528C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.*528C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001295087.1
TGFA	NM_001308159.2	c.*528C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001295088.1
TGFA	NM_001099691.3	c.*528C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.*528C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_003236.4	ENSP00000295400.6
TGFA	ENST00000418333.6	c.*528C>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000404099.2
TGFA	ENST00000445399.5	c.*19-710C>T		intron_variant	Intron 6 of 6	1		ENSP00000387493.1
TGFA	ENST00000419940.5	c.377-710C>T		intron_variant	Intron 3 of 3	5		ENSP00000407432.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35570 AN: 151912 Hom.: 4511 Cov.: 32

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: 90 AN: 600 Hom.: 9 Cov.: 0 AF XY: 0.135 AC XY: 43 AN XY: 318

African (AFR) AF: 0.00 AC: 0 AN: 12

American (AMR) AF: 0.100 AC: 8 AN: 80

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 1 AN: 10

East Asian (EAS) AF: 0.182 AC: 4 AN: 22

South Asian (SAS) AF: 0.0556 AC: 1 AN: 18

European-Finnish (FIN) AF: 0.292 AC: 7 AN: 24

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.157 AC: 64 AN: 408

Other (OTH) AF: 0.192 AC: 5 AN: 26

GnomAD4 genome AF: 0.234 AC: 35588 AN: 152030 Hom.: 4519 Cov.: 32 AF XY: 0.234 AC XY: 17382 AN XY: 74300

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: 53 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19024 AN: 67964

Other (OTH) AF: 0.234 AC: 493 AN: 2106

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.7
DANN	Benign	0.73
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1058213; hg19: chr2-70677463;