NM_003236.4:c.95-4799C>T

Variant names:

• chr2-70470535-G-A
• rs3771514
• NM_003236.4:c.95-4799C>T

Variant summary

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

The NM_003236.4(TGFA):​c.95-4799C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,168 control chromosomes in the GnomAD database, including 5,525 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 0.26 (5525 hom., cov: 32)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4	c.95-4799C>T		intron_variant	Intron 2 of 5	ENST00000295400.11	NP_003227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.95-4799C>T		intron_variant	Intron 2 of 5	1	NM_003236.4	ENSP00000295400.6

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39886 AN: 152050 Hom.: 5512 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.262 AC: 39943 AN: 152168 Hom.: 5525 Cov.: 32 AF XY: 0.263 AC XY: 19590 AN XY: 74398

African (AFR) AF: 0.329 AC: 13665 AN: 41484

American (AMR) AF: 0.315 AC: 4810 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3470

East Asian (EAS) AF: 0.173 AC: 897 AN: 5190

South Asian (SAS) AF: 0.199 AC: 962 AN: 4826

European-Finnish (FIN) AF: 0.283 AC: 2992 AN: 10586

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15277 AN: 68000

Other (OTH) AF: 0.238 AC: 503 AN: 2112

Alfa AF: 0.238 Hom.: 11604

Bravo AF: 0.269

Asia WGS AF: 0.212 AC: 741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.24
DANN	Benign	0.45
PhyloP100		-0.32
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: rs3771514; hg19: chr2-70697667;