rs473698

Variant names:

• chr2-70448449-C-G
• rs473698
• NM_003236.4:c.*2410G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-70448449-C-G
• chr2-70448449-C-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.*2410G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,026 control chromosomes in the GnomAD database, including 9,193 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 0.33 (9193 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TGFA NM_003236.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 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.*2410G>C		3_prime_UTR	Exon 6 of 6	NP_003227.1	P01135-1
	TGFA	NM_001308158.2		c.*2410G>C		3_prime_UTR	Exon 6 of 6	NP_001295087.1	F8VNR3
	TGFA	NM_001308159.2		c.*2410G>C		3_prime_UTR	Exon 6 of 6	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.*2410G>C		3_prime_UTR	Exon 6 of 6	ENSP00000295400.6	P01135-1
	TGFA	ENST00000869601.1		c.*2410G>C		3_prime_UTR	Exon 5 of 5	ENSP00000539660.1
	TGFA	ENST00000869602.1		c.*2410G>C		3_prime_UTR	Exon 5 of 5	ENSP00000539661.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50850 AN: 151906 Hom.: 9199 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.366

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.335 AC: 50856 AN: 152026 Hom.: 9193 Cov.: 32 AF XY: 0.331 AC XY: 24616 AN XY: 74328

African (AFR) AF: 0.219 AC: 9087 AN: 41458

American (AMR) AF: 0.350 AC: 5348 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1815 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1682 AN: 5176

South Asian (SAS) AF: 0.405 AC: 1948 AN: 4808

European-Finnish (FIN) AF: 0.286 AC: 3030 AN: 10578

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.394 AC: 26782 AN: 67968

Other (OTH) AF: 0.362 AC: 763 AN: 2108

Alfa AF: 0.343 Hom.: 1253

Bravo AF: 0.331

Asia WGS AF: 0.326 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.1
DANN	Benign	0.46
PhyloP100		0.028
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: rs473698; hg19: chr2-70675581;