2-70549252-T-C

Variant names:

• chr2-70549252-T-C
• rs12473408
• NM_003236.4:c.40+4476A>G

Variant summary

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

The NM_003236.4(TGFA):​c.40+4476A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,032 control chromosomes in the GnomAD database, including 18,842 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 0.49 (18842 hom., cov: 32)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4	c.40+4476A>G		intron_variant	Intron 1 of 5	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.58+3932A>G		intron_variant	Intron 1 of 5		NP_001295087.1
TGFA	NM_001308159.2	c.58+3932A>G		intron_variant	Intron 1 of 5		NP_001295088.1
TGFA	NM_001099691.3	c.40+4476A>G		intron_variant	Intron 1 of 5		NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.40+4476A>G		intron_variant	Intron 1 of 5	1	NM_003236.4	ENSP00000295400.6

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75044 AN: 151914 Hom.: 18805 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.494 AC: 75134 AN: 152032 Hom.: 18842 Cov.: 32 AF XY: 0.501 AC XY: 37193 AN XY: 74304

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.465

Alfa AF: 0.440 Hom.: 8787

Bravo AF: 0.489

Asia WGS AF: 0.543 AC: 1887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.22

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: rs12473408; hg19: chr2-70776384;