2-70505720-A-G

Position:

• chr2-70505720-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003236.4(TGFA):​c.94+9139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,856 control chromosomes in the GnomAD database, including 21,729 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 0.52 (21729 hom., cov: 31)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFA	NM_003236.4	c.94+9139T>C		intron_variant		ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.112+9139T>C		intron_variant			NP_001295087.1
TGFA	NM_001308159.2	c.112+9139T>C		intron_variant			NP_001295088.1
TGFA	NM_001099691.3	c.94+9139T>C		intron_variant			NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.94+9139T>C		intron_variant		1	NM_003236.4	ENSP00000295400.6

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78348 AN: 151740 Hom.: 21700 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.516 AC: 78429 AN: 151856 Hom.: 21729 Cov.: 31 AF XY: 0.511 AC XY: 37915 AN XY: 74208

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.496

Alfa AF: 0.430 Hom.: 15694

Bravo AF: 0.527

Asia WGS AF: 0.460 AC: 1598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.2
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs3755377; hg19: chr2-70732852;