rs538118

Variant names:

• chr2-70449507-A-C
• rs538118
• NM_003236.4:c.*1352T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-70449507-A-C
• chr2-70449507-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003236.4(TGFA):​c.*1352T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TGFA NM_003236.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 11 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 Gene-Disease associations (from GenCC):

• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFA	NM_003236.4	MANE Select	c.*1352T>G		3_prime_UTR	Exon 6 of 6	NP_003227.1
	TGFA	NM_001308158.2		c.*1352T>G		3_prime_UTR	Exon 6 of 6	NP_001295087.1
	TGFA	NM_001308159.2		c.*1352T>G		3_prime_UTR	Exon 6 of 6	NP_001295088.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFA	ENST00000295400.11	TSL:1 MANE Select	c.*1352T>G		3_prime_UTR	Exon 6 of 6	ENSP00000295400.6
	TGFA	ENST00000445399.5	TSL:1	c.*133T>G		3_prime_UTR	Exon 7 of 7	ENSP00000387493.1
	TGFA	ENST00000419940.5	TSL:5	c.*98T>G		3_prime_UTR	Exon 4 of 4	ENSP00000407432.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.071
DANN	Benign	0.46
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs538118; hg19: chr2-70676639;