rs2166975

Positions:

• chr2-70450862-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003236.4(TGFA):​c.480C>T​(p.Val160=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,607,768 control chromosomes in the GnomAD database, including 57,977 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 0.23 (4518 hom., cov: 32)
  • Exomes 𝑓: 0.27 (53459 hom.)
• Consequence: TGFA NM_003236.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=2.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFA	NM_003236.4	c.480C>T	p.Val160=	synonymous_variant	6/6	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.498C>T	p.Val166=	synonymous_variant	6/6		NP_001295087.1
TGFA	NM_001308159.2	c.495C>T	p.Val165=	synonymous_variant	6/6		NP_001295088.1
TGFA	NM_001099691.3	c.477C>T	p.Val159=	synonymous_variant	6/6		NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.480C>T	p.Val160=	synonymous_variant	6/6	1	NM_003236.4	ENSP00000295400	P4

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35557 AN: 151954 Hom.: 4510 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.240 AC: 58120 AN: 242456 Hom.: 7581 AF XY: 0.244 AC XY: 31952 AN XY: 130752

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.299

Gnomad SAS exome AF: 0.223

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.274

Gnomad OTH exome AF: 0.242

GnomAD4 exome AF: 0.267 AC: 388789 AN: 1455696 Hom.: 53459 Cov.: 33 AF XY: 0.266 AC XY: 192735 AN XY: 723506

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.280

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.234 AC: 35575 AN: 152072 Hom.: 4518 Cov.: 32 AF XY: 0.234 AC XY: 17378 AN XY: 74332

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.234

Alfa AF: 0.251 Hom.: 5414

Bravo AF: 0.220

Asia WGS AF: 0.287 AC: 999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.4
DANN	Benign	0.66

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: rs2166975; hg19: chr2-70677994; COSMIC: COSV54912701;