2-70450307-A-G

Variant names:

• chr2-70450307-A-G
• rs11466285
• NM_003236.4:c.*552T>C

Variant summary

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

The NM_003236.4(TGFA):​c.*552T>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 0.0862 in 152,756 control chromosomes in the GnomAD database, including 698 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 0.086 (696 hom., cov: 33)
  • Exomes 𝑓: 0.075 (2 hom.)
• Consequence: TGFA NM_003236.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4	c.*552T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.*552T>C		3_prime_UTR_variant	Exon 6 of 6		NP_001295087.1
TGFA	NM_001308159.2	c.*552T>C		3_prime_UTR_variant	Exon 6 of 6		NP_001295088.1
TGFA	NM_001099691.3	c.*552T>C		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.*552T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_003236.4	ENSP00000295400.6
TGFA	ENST00000418333	c.*552T>C		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000404099.2
TGFA	ENST00000445399.5	c.*19-686T>C		intron_variant	Intron 6 of 6	1		ENSP00000387493.1
TGFA	ENST00000419940.5	c.377-686T>C		intron_variant	Intron 3 of 3	5		ENSP00000407432.1

Frequencies

GnomAD3 genomes AF: 0.0862 AC: 13118 AN: 152156 Hom.: 696 Cov.: 33

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.0501

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0417

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0746

GnomAD4 exome AF: 0.0747 AC: 36 AN: 482 Hom.: 2 Cov.: 0 AF XY: 0.0672 AC XY: 18 AN XY: 268

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.0819

Gnomad4 OTH exome AF: 0.0455

GnomAD4 genome AF: 0.0862 AC: 13129 AN: 152274 Hom.: 696 Cov.: 33 AF XY: 0.0855 AC XY: 6362 AN XY: 74446

Gnomad4 AFR AF: 0.0471

Gnomad4 AMR AF: 0.0500

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0419

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0718 Hom.: 236

Bravo AF: 0.0773

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.6
DANN	Benign	0.78

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: rs11466285; hg19: chr2-70677439;