Variant 2-70514890-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003236.4(TGFA):c.63G>A(p.Gln21Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,614,062 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 16 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 26 hom. )

Consequence

TGFA
NM_003236.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.207

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:

TGFA (HGNC:):

TGFA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 2-70514890-C-T is Benign according to our data. Variant chr2-70514890-C-T is described in ClinVar as [Benign]. Clinvar id is 787233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.207 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00875 (1333/152340) while in subpopulation AFR AF= 0.0302 (1256/41572). AF 95% confidence interval is 0.0288. There are 16 homozygotes in gnomad4. There are 621 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1333 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFA	NM_003236.4 linkuse as main transcript	c.63G>A	p.Gln21Gln	synonymous_variant	2/6	ENST00000295400.11	NP_003227.1	P01135-1
TGFA	NM_001308158.2 linkuse as main transcript	c.81G>A	p.Gln27Gln	synonymous_variant	2/6		NP_001295087.1	P01135F8VNR3
TGFA	NM_001308159.2 linkuse as main transcript	c.81G>A	p.Gln27Gln	synonymous_variant	2/6		NP_001295088.1	P01135E7EPT6
TGFA	NM_001099691.3 linkuse as main transcript	c.63G>A	p.Gln21Gln	synonymous_variant	2/6		NP_001093161.1	P01135-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11 linkuse as main transcript	c.63G>A	p.Gln21Gln	synonymous_variant	2/6	1	NM_003236.4	ENSP00000295400.6		P01135-1

Frequencies

GnomAD3 genomes

AF:

0.00873

AC:

1329

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00248

AC:

622

AN:

250656

Hom.:

AF XY:

0.00197

AC XY:

267

AN XY:

135476

show subpopulations

Gnomad AFR exome

AF:

0.0324

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.00249

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000618

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000938

AC:

1371

AN:

1461722

Hom.:

Cov.:

AF XY:

0.000803

AC XY:

584

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.0309

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.00219

GnomAD4 genome

AF:

0.00875

AC:

1333

AN:

152340

Hom.:

Cov.:

AF XY:

0.00834

AC XY:

621

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0302

Gnomad4 AMR

AF:

0.00398

Gnomad4 ASJ

AF:

0.00230

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:

0.00414

Hom.:

Bravo

AF:

0.00991

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.53

CADD

Benign

2.4

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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