rs1880039

Variant names:

• chr2-70459920-A-G
• rs1880039
• NM_003236.4:c.216-3432T>C

Variant summary

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

The NM_003236.4(TGFA):​c.216-3432T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,126 control chromosomes in the GnomAD database, including 1,834 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 (1834 hom., cov: 32)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4	c.216-3432T>C		intron_variant	Intron 3 of 5	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.234-3432T>C		intron_variant	Intron 3 of 5		NP_001295087.1
TGFA	NM_001308159.2	c.231-3432T>C		intron_variant	Intron 3 of 5		NP_001295088.1
TGFA	NM_001099691.3	c.213-3432T>C		intron_variant	Intron 3 of 5		NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.216-3432T>C		intron_variant	Intron 3 of 5	1	NM_003236.4	ENSP00000295400.6

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22146 AN: 152008 Hom.: 1830 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0730

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.137

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.146 AC: 22186 AN: 152126 Hom.: 1834 Cov.: 32 AF XY: 0.149 AC XY: 11060 AN XY: 74374

African (AFR) AF: 0.167 AC: 6949 AN: 41508

American (AMR) AF: 0.261 AC: 3988 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3464

East Asian (EAS) AF: 0.0733 AC: 379 AN: 5168

South Asian (SAS) AF: 0.163 AC: 786 AN: 4814

European-Finnish (FIN) AF: 0.141 AC: 1496 AN: 10584

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7835 AN: 67996

Other (OTH) AF: 0.136 AC: 288 AN: 2110

Alfa AF: 0.138 Hom.: 1945

Bravo AF: 0.157

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.76
DANN	Benign	0.43
PhyloP100		-1.1
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: rs1880039; hg19: chr2-70687052;