rs503314

chr2-70447617-G-C

Variant summary

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

The NM_003236.4(TGFA):c.*3242C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,442 control chromosomes in the GnomAD database, including 10,302 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 0.36 (10291 hom., cov: 33)
  • Exomes 𝑓: 0.33 (11 hom.)
• Consequence: TGFA NM_003236.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFA	NM_003236.4	c.*3242C>G		3_prime_UTR_variant	6/6	ENST00000295400.11
TGFA	NM_001099691.3	c.*3242C>G		3_prime_UTR_variant	6/6
TGFA	NM_001308158.2	c.*3242C>G		3_prime_UTR_variant	6/6
TGFA	NM_001308159.2	c.*3242C>G		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFA	ENST00000295400.11	c.*3242C>G		3_prime_UTR_variant	6/6	1	NM_003236.4	P4

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54891 AN: 151964 Hom.: 10293 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.325 AC: 117 AN: 360 Hom.: 11 Cov.: 0 AF XY: 0.317 AC XY: 71 AN XY: 224

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.361 AC: 54910 AN: 152082 Hom.: 10291 Cov.: 33 AF XY: 0.357 AC XY: 26508 AN XY: 74340

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.389

Alfa AF: 0.361 Hom.: 1284

Bravo AF: 0.362

Asia WGS AF: 0.337 AC: 1168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.8
Dann	Benign	0.62

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: rs503314; hg19: chr2-70674749;