Variant 2-70514916-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003236.4(TGFA):c.41-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000513 in 1,613,660 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 4 hom. )

Consequence

TGFA
NM_003236.4 splice_region, intron

Scores

Splicing: ADA: 0.7986

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0370

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 2-70514916-T-C is Benign according to our data. Variant chr2-70514916-T-C is described in ClinVar as [Benign]. Clinvar id is 714126.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 436 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TGFA	NM_003236.4 link	c.41-4A>G	splice_region_variant, intron_variant	ENST00000295400.11	NP_003227.1	P01135-1
TGFA	NM_001308158.2 link	c.59-4A>G	splice_region_variant, intron_variant		NP_001295087.1	P01135F8VNR3
TGFA	NM_001308159.2 link	c.59-4A>G	splice_region_variant, intron_variant		NP_001295088.1	P01135E7EPT6
TGFA	NM_001099691.3 link	c.41-4A>G	splice_region_variant, intron_variant		NP_001093161.1	P01135-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11 link	c.41-4A>G		splice_region_variant, intron_variant		1	NM_003236.4	ENSP00000295400.6		P01135-1

Frequencies

GnomAD3 genomes

AF:

0.00287

AC:

436

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00978

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000813

AC:

203

AN:

249798

Hom.:

AF XY:

0.000496

AC XY:

AN XY:

134998

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.000639

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000268

AC:

392

AN:

1461422

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

150

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.00950

Gnomad4 AMR exome

AF:

0.000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.00286

AC:

436

AN:

152238

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00977

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00152

Hom.:

Bravo

AF:

0.00341

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.80

dbscSNV1_RF

Benign

0.61

SpliceAI score (max)

0.79

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.79

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over