2-70523399-T-C

Position:

• chr2-70523399-T-C

Variant summary

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

The NM_003236.4(TGFA):​c.41-8487A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,064 control chromosomes in the GnomAD database, including 9,015 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 0.30 (9015 hom., cov: 32)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFA	NM_003236.4	c.41-8487A>G		intron_variant		ENST00000295400.11
TGFA	NM_001099691.3	c.41-8487A>G		intron_variant
TGFA	NM_001308158.2	c.59-8487A>G		intron_variant
TGFA	NM_001308159.2	c.59-8487A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFA	ENST00000295400.11	c.41-8487A>G		intron_variant		1	NM_003236.4	P4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45057 AN: 151946 Hom.: 8985 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.297 AC: 45137 AN: 152064 Hom.: 9015 Cov.: 32 AF XY: 0.294 AC XY: 21890 AN XY: 74372

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.273

Alfa AF: 0.192 Hom.: 5737

Bravo AF: 0.313

Asia WGS AF: 0.219 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.020
DANN	Benign	0.50

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: rs426081; hg19: chr2-70750531;