2-70489467-T-C

Position:

• chr2-70489467-T-C

Variant summary

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

The NM_003236.4(TGFA):​c.95-23731A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,138 control chromosomes in the GnomAD database, including 25,297 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 0.57 (25297 hom., cov: 33)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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 (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 (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFA	NM_003236.4	c.95-23731A>G		intron_variant		ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.113-23731A>G		intron_variant			NP_001295087.1
TGFA	NM_001308159.2	c.113-23734A>G		intron_variant			NP_001295088.1
TGFA	NM_001099691.3	c.95-23734A>G		intron_variant			NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.95-23731A>G		intron_variant		1	NM_003236.4	ENSP00000295400.6

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86972 AN: 152020 Hom.: 25270 Cov.: 33

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.572 AC: 87048 AN: 152138 Hom.: 25297 Cov.: 33 AF XY: 0.573 AC XY: 42598 AN XY: 74354

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.563

Alfa AF: 0.572 Hom.: 3525

Bravo AF: 0.581

Asia WGS AF: 0.564 AC: 1963 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	0.70
DANN	Benign	0.29

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: rs2902345; hg19: chr2-70716599;