rs11466191

chr2-70552949-C-G

Variant summary

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

The NM_003236.4(TGFA):c.40+779G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,126 control chromosomes in the GnomAD database, including 5,589 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 0.27 (5589 hom., cov: 33)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

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]

LOC124907824 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFA	NM_003236.4	c.40+779G>C		intron_variant		ENST00000295400.11
LOC124907824	XR_007086906.1	n.242C>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFA	ENST00000295400.11	c.40+779G>C		intron_variant		1	NM_003236.4	P4

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40670 AN: 152008 Hom.: 5571 Cov.: 33

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.268 AC: 40725 AN: 152126 Hom.: 5589 Cov.: 33 AF XY: 0.270 AC XY: 20079 AN XY: 74388

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.276

Alfa AF: 0.259 Hom.: 673

Bravo AF: 0.277

Asia WGS AF: 0.302 AC: 1049 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	6.4
Dann	Benign	0.63

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: rs11466191; hg19: chr2-70780081;