2-70477379-A-G

Variant names:

• chr2-70477379-A-G
• rs3755384
• NM_003236.4:c.95-11643T>C

Variant summary

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

The NM_001308158.2(TGFA):​c.113-11643T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,038 control chromosomes in the GnomAD database, including 24,408 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 0.56 (24408 hom., cov: 32)
• Consequence: TGFA NM_001308158.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308158.2. 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.95-11643T>C		intron	N/A	NP_003227.1
	TGFA	NM_001308158.2		c.113-11643T>C		intron	N/A	NP_001295087.1
	TGFA	NM_001308159.2		c.113-11646T>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.95-11643T>C		intron	N/A	ENSP00000295400.6
	TGFA	ENST00000444975.5	TSL:1	c.113-11643T>C		intron	N/A	ENSP00000404131.1
	TGFA	ENST00000450929.5	TSL:1	c.113-11646T>C		intron	N/A	ENSP00000414127.1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85354 AN: 151920 Hom.: 24382 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.562 AC: 85429 AN: 152038 Hom.: 24408 Cov.: 32 AF XY: 0.562 AC XY: 41753 AN XY: 74302

African (AFR) AF: 0.652 AC: 27051 AN: 41474

American (AMR) AF: 0.584 AC: 8917 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3470

East Asian (EAS) AF: 0.609 AC: 3152 AN: 5172

South Asian (SAS) AF: 0.512 AC: 2463 AN: 4812

European-Finnish (FIN) AF: 0.544 AC: 5739 AN: 10558

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34956 AN: 67974

Other (OTH) AF: 0.555 AC: 1169 AN: 2106

Alfa AF: 0.497 Hom.: 8514

Bravo AF: 0.574

Asia WGS AF: 0.561 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.35
DANN	Benign	0.65
PhyloP100		0.0
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: rs3755384; hg19: chr2-70704511;