chr2-70448575-T-G

Position:

• chr2-70448575-T-G

Variant summary

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

The NM_003236.4(TGFA):​c.*2284A>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 0.0619 in 152,264 control chromosomes in the GnomAD database, including 430 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 0.062 (430 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TGFA NM_003236.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFA	NM_003236.4	c.*2284A>C		3_prime_UTR_variant	6/6	ENST00000295400.11
TGFA	NM_001099691.3	c.*2284A>C		3_prime_UTR_variant	6/6
TGFA	NM_001308158.2	c.*2284A>C		3_prime_UTR_variant	6/6
TGFA	NM_001308159.2	c.*2284A>C		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFA	ENST00000295400.11	c.*2284A>C		3_prime_UTR_variant	6/6	1	NM_003236.4	P4

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9434 AN: 152146 Hom.: 430 Cov.: 33

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0975

Gnomad OTH AF: 0.0503

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0619 AC: 9430 AN: 152264 Hom.: 430 Cov.: 33 AF XY: 0.0614 AC XY: 4568 AN XY: 74454

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0975

Gnomad4 OTH AF: 0.0498

Alfa AF: 0.0815 Hom.: 623

Bravo AF: 0.0552

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.74

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: rs11466297; hg19: chr2-70675707;