chr2-70467751-A-G

Variant names:

• chr2-70467751-A-G
• rs3771516
• NM_003236.4:c.95-2015T>C

Variant summary

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

The NM_003236.4(TGFA):​c.95-2015T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,234 control chromosomes in the GnomAD database, including 2,238 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 0.16 (2238 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 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.95-2015T>C		intron	N/A	NP_003227.1
	TGFA	NM_001308158.2		c.113-2015T>C		intron	N/A	NP_001295087.1
	TGFA	NM_001308159.2		c.113-2018T>C		intron	N/A	NP_001295088.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFA	ENST00000295400.11	TSL:1 MANE Select	c.95-2015T>C		intron	N/A	ENSP00000295400.6
	TGFA	ENST00000444975.5	TSL:1	c.113-2015T>C		intron	N/A	ENSP00000404131.1
	TGFA	ENST00000450929.5	TSL:1	c.113-2018T>C		intron	N/A	ENSP00000414127.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23590 AN: 152116 Hom.: 2233 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0424

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.155 AC: 23618 AN: 152234 Hom.: 2238 Cov.: 32 AF XY: 0.152 AC XY: 11316 AN XY: 74440

African (AFR) AF: 0.263 AC: 10909 AN: 41504

American (AMR) AF: 0.121 AC: 1852 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3472

East Asian (EAS) AF: 0.177 AC: 914 AN: 5174

South Asian (SAS) AF: 0.0427 AC: 206 AN: 4828

European-Finnish (FIN) AF: 0.142 AC: 1506 AN: 10612

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7591 AN: 68024

Other (OTH) AF: 0.134 AC: 283 AN: 2112

Alfa AF: 0.162 Hom.: 404

Bravo AF: 0.161

Asia WGS AF: 0.110 AC: 382 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.0
DANN	Benign	0.84
PhyloP100		0.31
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: rs3771516; hg19: chr2-70694883; COSMIC: COSV54916761; COSMIC: COSV54916761;