rs3771516

chr2-70467751-A-G

Variant summary

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

The NM_003236.4(TGFA):c.95-2015T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,234 control chromosomes in the GnomAD database, including 2,238 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 0.16 (2238 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

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:41389): (TGFA intronic transcript 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFA	NM_003236.4	c.95-2015T>C		intron_variant		ENST00000295400.11
TGFA-IT1	NR_046798.1	n.181-55T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFA	ENST00000295400.11	c.95-2015T>C		intron_variant		1	NM_003236.4	P4
TGFA-IT1	ENST00000441238.1	n.125-55T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23590 AN: 152116 Hom.: 2233 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0424

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.155 AC: 23618 AN: 152234 Hom.: 2238 Cov.: 32 AF XY: 0.152 AC XY: 11316 AN XY: 74440

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.0427

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.134

Alfa AF: 0.159 Hom.: 371

Bravo AF: 0.161

Asia WGS AF: 0.110 AC: 382 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	9.0
Dann	Benign	0.84

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: rs3771516; hg19: chr2-70694883; COSMIC: COSV54916761; COSMIC: COSV54916761;