5-136029203-C-A

Position:

chr5-136029203-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_000358.3(TGFBI):c.134+14C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,472,572 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 18 hom. )

Consequence

TGFBI
NM_000358.3 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.0430

Variant links:

Genes affected

TGFBI (HGNC:11771): (transforming growth factor beta induced) This gene encodes an RGD-containing protein that binds to type I, II and IV collagens. The RGD motif is found in many extracellular matrix proteins modulating cell adhesion and serves as a ligand recognition sequence for several integrins. This protein plays a role in cell-collagen interactions and may be involved in endochondrial bone formation in cartilage. The protein is induced by transforming growth factor-beta and acts to inhibit cell adhesion. Mutations in this gene are associated with multiple types of corneal dystrophy. [provided by RefSeq, Jul 2008]

TGFBI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 5-136029203-C-A is Benign according to our data. Variant chr5-136029203-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 350866.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00285 (434/152294) while in subpopulation NFE AF= 0.00547 (372/68014). AF 95% confidence interval is 0.00501. There are 1 homozygotes in gnomad4. There are 189 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 434 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBI	NM_000358.3 linkuse as main transcript	c.134+14C>A		intron_variant		ENST00000442011.7	NP_000349.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
TGFBI	ENST00000442011.7 linkuse as main transcript	c.134+14C>A	intron_variant	1	NM_000358.3	ENSP00000416330	P1
TGFBI	ENST00000507018.5 linkuse as main transcript	c.51+14C>A	intron_variant, NMD_transcript_variant	5		ENSP00000421540
TGFBI	ENST00000504185.5 linkuse as main transcript	n.202+14C>A	intron_variant, non_coding_transcript_variant	4
TGFBI	ENST00000506699.5 linkuse as main transcript	n.199+14C>A	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

434

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00547

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00298

AC:

226

AN:

75720

Hom.:

AF XY:

0.00273

AC XY:

116

AN XY:

42454

show subpopulations

Gnomad AFR exome

AF:

0.00226

Gnomad AMR exome

AF:

0.000804

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00130

Gnomad FIN exome

AF:

0.00137

Gnomad NFE exome

AF:

0.00630

Gnomad OTH exome

AF:

0.00387

GnomAD4 exome

AF:

0.00476

AC:

6291

AN:

1320278

Hom.:

Cov.:

AF XY:

0.00460

AC XY:

2976

AN XY:

646936

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.000904

Gnomad4 ASJ exome

AF:

0.0000896

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00132

Gnomad4 FIN exome

AF:

0.00213

Gnomad4 NFE exome

AF:

0.00560

Gnomad4 OTH exome

AF:

0.00389

GnomAD4 genome

AF:

0.00285

AC:

434

AN:

152294

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

189

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00547

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.00268

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Corneal dystrophy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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