2-70530226-A-G

Variant names:

• chr2-70530226-A-G
• rs11466212
• NM_003236.4:c.41-15314T>C

Variant summary

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

The NM_003236.4(TGFA):​c.41-15314T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0951 in 152,318 control chromosomes in the GnomAD database, including 981 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 0.095 (981 hom., cov: 33)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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 (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4	c.41-15314T>C		intron_variant	Intron 1 of 5	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.59-15314T>C		intron_variant	Intron 1 of 5		NP_001295087.1
TGFA	NM_001308159.2	c.59-15314T>C		intron_variant	Intron 1 of 5		NP_001295088.1
TGFA	NM_001099691.3	c.41-15314T>C		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.41-15314T>C		intron_variant	Intron 1 of 5	1	NM_003236.4	ENSP00000295400.6

Frequencies

GnomAD3 genomes AF: 0.0951 AC: 14474 AN: 152200 Hom.: 975 Cov.: 33

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.0993

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

GnomAD4 genome AF: 0.0951 AC: 14482 AN: 152318 Hom.: 981 Cov.: 33 AF XY: 0.0998 AC XY: 7432 AN XY: 74486

Gnomad4 AFR AF: 0.0290

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.0945

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0961

Gnomad4 OTH AF: 0.0978

Alfa AF: 0.101 Hom.: 1077

Bravo AF: 0.0999

Asia WGS AF: 0.147 AC: 511 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	3.8
DANN	Benign	0.59

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: rs11466212; hg19: chr2-70757358;