2-70471724-C-T

Variant names:

• chr2-70471724-C-T
• rs1523305
• NM_003236.4:c.95-5988G>A

Variant summary

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

The NM_003236.4(TGFA):​c.95-5988G>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
• Publications: 12 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 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.95-5988G>A		intron	N/A	NP_003227.1	P01135-1
	TGFA	NM_001308158.2		c.113-5988G>A		intron	N/A	NP_001295087.1	F8VNR3
	TGFA	NM_001308159.2		c.113-5991G>A		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.95-5988G>A		intron	N/A	ENSP00000295400.6	P01135-1
	TGFA	ENST00000444975.5	TSL:1	c.113-5988G>A		intron	N/A	ENSP00000404131.1	F8VNR3
	TGFA	ENST00000450929.5	TSL:1	c.113-5991G>A		intron	N/A	ENSP00000414127.1	E7EPT6

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

African (AFR) AF: 0.519 AC: 21486 AN: 41400

American (AMR) AF: 0.561 AC: 8572 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1311 AN: 3472

East Asian (EAS) AF: 0.586 AC: 3018 AN: 5152

South Asian (SAS) AF: 0.502 AC: 2415 AN: 4806

European-Finnish (FIN) AF: 0.527 AC: 5555 AN: 10542

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34048 AN: 67932

Other (OTH) AF: 0.519 AC: 1089 AN: 2100

Alfa AF: 0.523 Hom.: 4076

Bravo AF: 0.523

Asia WGS AF: 0.542 AC: 1889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.46
PhyloP100		-0.15
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1523305; hg19: chr2-70698856;