chr2-70447450-A-T

Variant names:

• chr2-70447450-A-T
• rs3771527
• NM_003236.4:c.*3409T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003236.4(TGFA):​c.*3409T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,680 control chromosomes in the GnomAD database, including 1,971 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 0.15 (1964 hom., cov: 33)
  • Exomes 𝑓: 0.17 (7 hom.)
• Consequence: TGFA NM_003236.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• Publications: 9 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.263 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFA	NM_003236.4	MANE Select	c.*3409T>A		3_prime_UTR	Exon 6 of 6	NP_003227.1
	TGFA	NM_001308158.2		c.*3409T>A		3_prime_UTR	Exon 6 of 6	NP_001295087.1
	TGFA	NM_001308159.2		c.*3409T>A		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.*3409T>A		3_prime_UTR	Exon 6 of 6	ENSP00000295400.6

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22407 AN: 152138 Hom.: 1961 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.171 AC: 73 AN: 426 Hom.: 7 Cov.: 0 AF XY: 0.171 AC XY: 44 AN XY: 258

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.171 AC: 72 AN: 420

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.147 AC: 22422 AN: 152254 Hom.: 1964 Cov.: 33 AF XY: 0.153 AC XY: 11373 AN XY: 74440

African (AFR) AF: 0.141 AC: 5855 AN: 41558

American (AMR) AF: 0.269 AC: 4122 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 363 AN: 3472

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

South Asian (SAS) AF: 0.169 AC: 814 AN: 4816

European-Finnish (FIN) AF: 0.189 AC: 1997 AN: 10590

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7963 AN: 68010

Other (OTH) AF: 0.139 AC: 294 AN: 2116

Alfa AF: 0.109 Hom.: 166

Bravo AF: 0.155

Asia WGS AF: 0.170 AC: 590 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3771527; hg19: chr2-70674582;