2-70552949-C-G

Variant names:

• chr2-70552949-C-G
• rs11466191
• NM_003236.4:c.40+779G>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.40+779G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,126 control chromosomes in the GnomAD database, including 5,589 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 0.27 (5589 hom., cov: 33)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• Publications: 12 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

ENSG00000294870 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4	c.40+779G>C		intron_variant	Intron 1 of 5	ENST00000295400.11	NP_003227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.40+779G>C		intron_variant	Intron 1 of 5	1	NM_003236.4	ENSP00000295400.6

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40670 AN: 152008 Hom.: 5571 Cov.: 33

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.268 AC: 40725 AN: 152126 Hom.: 5589 Cov.: 33 AF XY: 0.270 AC XY: 20079 AN XY: 74388

African (AFR) AF: 0.285 AC: 11835 AN: 41488

American (AMR) AF: 0.337 AC: 5157 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1053 AN: 3466

East Asian (EAS) AF: 0.238 AC: 1229 AN: 5166

South Asian (SAS) AF: 0.344 AC: 1656 AN: 4816

European-Finnish (FIN) AF: 0.233 AC: 2470 AN: 10606

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16358 AN: 67978

Other (OTH) AF: 0.276 AC: 582 AN: 2112

Alfa AF: 0.259 Hom.: 673

Bravo AF: 0.277

Asia WGS AF: 0.302 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.4
DANN	Benign	0.63
PhyloP100		-0.25
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: rs11466191; hg19: chr2-70780081;