rs473698

chr2-70448449-C-Gchr2-70448449-C-T

Variant summary

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

The NM_003236.4(TGFA):c.*2410G>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 0.335 in 152,026 control chromosomes in the GnomAD database, including 9,193 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 0.33 (9193 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TGFA NM_003236.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

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=-0.91).
• 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	UniProt
TGFA	NM_003236.4	c.*2410G>C		3_prime_UTR_variant	6/6	ENST00000295400.11
TGFA	NM_001099691.3	c.*2410G>C		3_prime_UTR_variant	6/6
TGFA	NM_001308158.2	c.*2410G>C		3_prime_UTR_variant	6/6
TGFA	NM_001308159.2	c.*2410G>C		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFA	ENST00000295400.11	c.*2410G>C		3_prime_UTR_variant	6/6	1	NM_003236.4	P4

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50850 AN: 151906 Hom.: 9199 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.335 AC: 50856 AN: 152026 Hom.: 9193 Cov.: 32 AF XY: 0.331 AC XY: 24616 AN XY: 74328

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.362

Alfa AF: 0.343 Hom.: 1253

Bravo AF: 0.331

Asia WGS AF: 0.326 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	8.1
Dann	Benign	0.46

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: rs473698; hg19: chr2-70675581;