chr2-70457319-A-G

Variant names:

• chr2-70457319-A-G
• rs930655
• NM_003236.4:c.216-831T>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.216-831T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,904 control chromosomes in the GnomAD database, including 33,420 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 0.65 (33420 hom., cov: 30)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4	c.216-831T>C		intron_variant	Intron 3 of 5	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.234-831T>C		intron_variant	Intron 3 of 5		NP_001295087.1
TGFA	NM_001308159.2	c.231-831T>C		intron_variant	Intron 3 of 5		NP_001295088.1
TGFA	NM_001099691.3	c.213-831T>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.216-831T>C		intron_variant	Intron 3 of 5	1	NM_003236.4	ENSP00000295400.6

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98509 AN: 151786 Hom.: 33366 Cov.: 30

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.649 AC: 98624 AN: 151904 Hom.: 33420 Cov.: 30 AF XY: 0.650 AC XY: 48235 AN XY: 74200

African (AFR) AF: 0.846 AC: 35073 AN: 41468

American (AMR) AF: 0.589 AC: 8995 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1397 AN: 3462

East Asian (EAS) AF: 0.601 AC: 3089 AN: 5140

South Asian (SAS) AF: 0.572 AC: 2748 AN: 4804

European-Finnish (FIN) AF: 0.661 AC: 6946 AN: 10516

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38334 AN: 67940

Other (OTH) AF: 0.607 AC: 1278 AN: 2104

Alfa AF: 0.576 Hom.: 76423

Bravo AF: 0.652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.39
PhyloP100		-0.038
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: rs930655; hg19: chr2-70684451;