chr2-70447450-A-T

Position:

• chr2-70447450-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003236.4(TGFA):​c.*3409T>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 0.147 in 152,680 control chromosomes in the GnomAD database, including 1,971 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 0.15 (1964 hom., cov: 33)
  • Exomes 𝑓: 0.17 (7 hom.)
• Consequence: TGFA NM_003236.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFA	NM_003236.4	c.*3409T>A		3_prime_UTR_variant	6/6	ENST00000295400.11	NP_003227.1
TGFA	NM_001099691.3	c.*3409T>A		3_prime_UTR_variant	6/6		NP_001093161.1
TGFA	NM_001308158.2	c.*3409T>A		3_prime_UTR_variant	6/6		NP_001295087.1
TGFA	NM_001308159.2	c.*3409T>A		3_prime_UTR_variant	6/6		NP_001295088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.*3409T>A		3_prime_UTR_variant	6/6	1	NM_003236.4	ENSP00000295400	P4

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22407 AN: 152138 Hom.: 1961 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.171 AC: 73 AN: 426 Hom.: 7 Cov.: 0 AF XY: 0.171 AC XY: 44 AN XY: 258

Gnomad4 FIN exome AF: 0.171

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.147 AC: 22422 AN: 152254 Hom.: 1964 Cov.: 33 AF XY: 0.153 AC XY: 11373 AN XY: 74440

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.139

Alfa AF: 0.109 Hom.: 166

Bravo AF: 0.155

Asia WGS AF: 0.170 AC: 590 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.84
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: rs3771527; hg19: chr2-70674582;