2-70471724-C-T

Position:

• chr2-70471724-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.95-5988G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,884 control chromosomes in the GnomAD database, including 20,256 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 0.51 (20256 hom., cov: 31)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

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]

TGFA-IT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFA	NM_003236.4	c.95-5988G>A		intron_variant		ENST00000295400.11	NP_003227.1
TGFA-IT1	NR_046798.1	n.57-3229G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.95-5988G>A		intron_variant		1	NM_003236.4	ENSP00000295400	P4

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78090 AN: 151766 Hom.: 20240 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.513

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.515 AC: 78146 AN: 151884 Hom.: 20256 Cov.: 31 AF XY: 0.516 AC XY: 38252 AN XY: 74192

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.519

Alfa AF: 0.523 Hom.: 3975

Bravo AF: 0.523

Asia WGS AF: 0.542 AC: 1889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
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: rs1523305; hg19: chr2-70698856;