2-70485109-A-G

Variant names:

• chr2-70485109-A-G
• rs3771503
• NM_003236.4:c.95-19373T>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.95-19373T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,028 control chromosomes in the GnomAD database, including 16,721 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 0.47 (16721 hom., cov: 32)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 2 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4	c.95-19373T>C		intron_variant	Intron 2 of 5	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.113-19373T>C		intron_variant	Intron 2 of 5		NP_001295087.1
TGFA	NM_001308159.2	c.113-19376T>C		intron_variant	Intron 2 of 5		NP_001295088.1
TGFA	NM_001099691.3	c.95-19376T>C		intron_variant	Intron 2 of 5		NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.95-19373T>C		intron_variant	Intron 2 of 5	1	NM_003236.4	ENSP00000295400.6

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70826 AN: 151908 Hom.: 16695 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.466 AC: 70884 AN: 152028 Hom.: 16721 Cov.: 32 AF XY: 0.468 AC XY: 34770 AN XY: 74302

African (AFR) AF: 0.443 AC: 18361 AN: 41448

American (AMR) AF: 0.509 AC: 7781 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1174 AN: 3466

East Asian (EAS) AF: 0.582 AC: 3011 AN: 5172

South Asian (SAS) AF: 0.423 AC: 2034 AN: 4812

European-Finnish (FIN) AF: 0.521 AC: 5502 AN: 10560

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31488 AN: 67972

Other (OTH) AF: 0.457 AC: 966 AN: 2112

Alfa AF: 0.460 Hom.: 2041

Bravo AF: 0.473

Asia WGS AF: 0.502 AC: 1748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.5
DANN	Benign	0.80
PhyloP100		1.3
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: rs3771503; hg19: chr2-70712241;