2-70449507-A-G

Position:

• chr2-70449507-A-G

Variant summary

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

The NM_003236.4(TGFA):​c.*1352T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 174,308 control chromosomes in the GnomAD database, including 11,056 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 0.34 (9217 hom., cov: 32)
  • Exomes 𝑓: 0.38 (1839 hom.)
• Consequence: TGFA NM_003236.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFA	NM_003236.4	c.*1352T>C		3_prime_UTR_variant	6/6	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.*1352T>C		3_prime_UTR_variant	6/6		NP_001295087.1
TGFA	NM_001308159.2	c.*1352T>C		3_prime_UTR_variant	6/6		NP_001295088.1
TGFA	NM_001099691.3	c.*1352T>C		3_prime_UTR_variant	6/6		NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.*1352T>C		3_prime_UTR_variant	6/6	1	NM_003236.4	ENSP00000295400.6
TGFA	ENST00000445399.5	c.*133T>C		3_prime_UTR_variant	7/7	1		ENSP00000387493.1
TGFA	ENST00000419940.5	c.*98T>C		3_prime_UTR_variant	4/4	5		ENSP00000407432.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50988 AN: 151924 Hom.: 9223 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.383 AC: 8531 AN: 22266 Hom.: 1839 Cov.: 0 AF XY: 0.389 AC XY: 4812 AN XY: 12374

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.331

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.378

Gnomad4 OTH exome AF: 0.395

GnomAD4 genome AF: 0.335 AC: 50994 AN: 152042 Hom.: 9217 Cov.: 32 AF XY: 0.332 AC XY: 24668 AN XY: 74320

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.363

Alfa AF: 0.402 Hom.: 12503

Bravo AF: 0.333

Asia WGS AF: 0.326 AC: 1132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.076
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs538118; hg19: chr2-70676639; COSMIC: COSV54915383; COSMIC: COSV54915383;