Variant 1-203348034-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_002023.5(FMOD):c.237G>A(p.Glu79Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 1,610,684 control chromosomes in the GnomAD database, including 520,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.68 ( 39237 hom., cov: 31)

Exomes 𝑓: 0.81 ( 481416 hom. )

Consequence

FMOD
NM_002023.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.576

Variant links:

Genes affected

FMOD (HGNC:3774): (fibromodulin) Fibromodulin belongs to the family of small interstitial proteoglycans. The encoded protein possesses a central region containing leucine-rich repeats with 4 keratan sulfate chains, flanked by terminal domains containing disulphide bonds. Owing to the interaction with type I and type II collagen fibrils and in vitro inhibition of fibrillogenesis, the encoded protein may play a role in the assembly of extracellular matrix. It may also regulate TGF-beta activities by sequestering TGF-beta into the extracellular matrix. Sequence variations in this gene may be associated with the pathogenesis of high myopia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

FMOD links:

FMOD (HGNC:):

FMOD links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 1-203348034-C-T is Benign according to our data. Variant chr1-203348034-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.576 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMOD	NM_002023.5 linkuse as main transcript	c.237G>A	p.Glu79Glu	synonymous_variant	2/3	ENST00000354955.5	NP_002014.2	Q06828A0A024R971Q12833B3KS64
FMOD	XM_047416304.1 linkuse as main transcript	c.237G>A	p.Glu79Glu	synonymous_variant	3/4		XP_047272260.1
FMOD	NR_103757.2 linkuse as main transcript	n.90+2999G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMOD	ENST00000354955.5 linkuse as main transcript	c.237G>A	p.Glu79Glu	synonymous_variant	2/3	1	NM_002023.5	ENSP00000347041.4		Q06828

Frequencies

GnomAD3 genomes

AF:

0.684

AC:

103911

AN:

151936

Hom.:

39239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.772

Gnomad AMR

AF:

0.761

Gnomad ASJ

AF:

0.780

Gnomad EAS

AF:

0.645

Gnomad SAS

AF:

0.714

Gnomad FIN

AF:

0.880

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.840

Gnomad OTH

AF:

0.710

GnomAD3 exomes

AF:

0.765

AC:

189683

AN:

247858

Hom.:

74774

AF XY:

0.774

AC XY:

103681

AN XY:

133872

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.749

Gnomad ASJ exome

AF:

0.788

Gnomad EAS exome

AF:

0.651

Gnomad SAS exome

AF:

0.729

Gnomad FIN exome

AF:

0.877

Gnomad NFE exome

AF:

0.838

Gnomad OTH exome

AF:

0.799

GnomAD4 exome

AF:

0.807

AC:

1177366

AN:

1458630

Hom.:

481416

Cov.:

AF XY:

0.807

AC XY:

585013

AN XY:

725220

show subpopulations

Gnomad4 AFR exome

AF:

0.312

Gnomad4 AMR exome

AF:

0.751

Gnomad4 ASJ exome

AF:

0.790

Gnomad4 EAS exome

AF:

0.621

Gnomad4 SAS exome

AF:

0.732

Gnomad4 FIN exome

AF:

0.871

Gnomad4 NFE exome

AF:

0.836

Gnomad4 OTH exome

AF:

0.777

GnomAD4 genome

AF:

0.684

AC:

103936

AN:

152054

Hom.:

39237

Cov.:

AF XY:

0.688

AC XY:

51170

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.337

Gnomad4 AMR

AF:

0.761

Gnomad4 ASJ

AF:

0.780

Gnomad4 EAS

AF:

0.645

Gnomad4 SAS

AF:

0.713

Gnomad4 FIN

AF:

0.880

Gnomad4 NFE

AF:

0.840

Gnomad4 OTH

AF:

0.711

Alfa

AF:

0.808

Hom.:

111790

Bravo

AF:

0.656

Asia WGS

AF:

0.662

AC:

2303

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

6.0

DANN

Benign

0.84

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over