2-70476898-C-G

Variant names:

• chr2-70476898-C-G
• rs958686
• NM_003236.4:c.95-11162G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003236.4(TGFA):​c.95-11162G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,090 control chromosomes in the GnomAD database, including 19,203 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 0.50 (19203 hom., cov: 33)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003236.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFA	NM_003236.4	MANE Select	c.95-11162G>C		intron	N/A	NP_003227.1	P01135-1
	TGFA	NM_001308158.2		c.113-11162G>C		intron	N/A	NP_001295087.1	F8VNR3
	TGFA	NM_001308159.2		c.113-11165G>C		intron	N/A	NP_001295088.1	E7EPT6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFA	ENST00000295400.11	TSL:1 MANE Select	c.95-11162G>C		intron	N/A	ENSP00000295400.6	P01135-1
	TGFA	ENST00000444975.5	TSL:1	c.113-11162G>C		intron	N/A	ENSP00000404131.1	F8VNR3
	TGFA	ENST00000450929.5	TSL:1	c.113-11165G>C		intron	N/A	ENSP00000414127.1	E7EPT6

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75852 AN: 151972 Hom.: 19174 Cov.: 33

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.499 AC: 75923 AN: 152090 Hom.: 19203 Cov.: 33 AF XY: 0.500 AC XY: 37148 AN XY: 74340

African (AFR) AF: 0.559 AC: 23219 AN: 41508

American (AMR) AF: 0.520 AC: 7940 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1177 AN: 3470

East Asian (EAS) AF: 0.582 AC: 3019 AN: 5186

South Asian (SAS) AF: 0.422 AC: 2031 AN: 4814

European-Finnish (FIN) AF: 0.521 AC: 5512 AN: 10578

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.463 AC: 31447 AN: 67954

Other (OTH) AF: 0.481 AC: 1011 AN: 2104

Alfa AF: 0.477 Hom.: 2102

Bravo AF: 0.510

Asia WGS AF: 0.505 AC: 1759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.57
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs958686; hg19: chr2-70704030;