chr2-70448966-G-A

Variant names:

• chr2-70448966-G-A
• rs3732253
• NM_003236.4:c.*1893C>T

Variant summary

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

The NM_003236.4(TGFA):​c.*1893C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,122 control chromosomes in the GnomAD database, including 4,293 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 0.22 (4293 hom., cov: 33)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: TGFA NM_003236.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4	c.*1893C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.*1893C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001295087.1
TGFA	NM_001308159.2	c.*1893C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001295088.1
TGFA	NM_001099691.3	c.*1893C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400	c.*1893C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_003236.4	ENSP00000295400.6

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34016 AN: 151994 Hom.: 4285 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.224 AC: 34029 AN: 152112 Hom.: 4293 Cov.: 33 AF XY: 0.224 AC XY: 16649 AN XY: 74352

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.223

Alfa AF: 0.252 Hom.: 3710

Bravo AF: 0.208

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.41
DANN	Benign	0.76

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: rs3732253; hg19: chr2-70676098;