rs3771523

chr2-70450336-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.*523G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,746 control chromosomes in the GnomAD database, including 1,767 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 0.14 (1754 hom., cov: 32)
  • Exomes 𝑓: 0.15 (13 hom.)
• Consequence: TGFA NM_003236.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.27

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 (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFA	NM_003236.4	c.*523G>A		3_prime_UTR_variant	6/6	ENST00000295400.11
TGFA	NM_001099691.3	c.*523G>A		3_prime_UTR_variant	6/6
TGFA	NM_001308158.2	c.*523G>A		3_prime_UTR_variant	6/6
TGFA	NM_001308159.2	c.*523G>A		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFA	ENST00000295400.11	c.*523G>A		3_prime_UTR_variant	6/6	1	NM_003236.4	P4
TGFA	ENST00000418333.6	c.*523G>A		3_prime_UTR_variant	6/6	1		A1
TGFA	ENST00000445399.5	c.*19-715G>A		intron_variant		1		A1
TGFA	ENST00000419940.5	c.379-715G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20983 AN: 151970 Hom.: 1753 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.150 AC: 99 AN: 658 Hom.: 13 Cov.: 0 AF XY: 0.157 AC XY: 56 AN XY: 356

Gnomad4 AFR exome AF: 0.0556

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.0833

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.138 AC: 20998 AN: 152088 Hom.: 1754 Cov.: 32 AF XY: 0.144 AC XY: 10687 AN XY: 74332

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.132

Alfa AF: 0.152 Hom.: 686

Bravo AF: 0.145

Asia WGS AF: 0.163 AC: 570 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	0.12
Dann	Benign	0.51

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: rs3771523; hg19: chr2-70677468;