Genetic Variant FMOD:p.Glu79Glu (chr1-203348034-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.028).

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 rank	MANE	Protein	UniProt
FMOD	NM_002023.5 link	c.237G>A	p.Glu79Glu	synonymous_variant	Exon 2 of 3	ENST00000354955.5	NP_002014.2	Q06828A0A024R971Q12833B3KS64
FMOD	XM_047416304.1 link	c.237G>A	p.Glu79Glu	synonymous_variant	Exon 3 of 4		XP_047272260.1
FMOD	NR_103757.2 link	n.90+2999G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMOD	ENST00000354955.5 link	c.237G>A	p.Glu79Glu	synonymous_variant	Exon 2 of 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

GnomAD2 exomes

AF:

0.765

AC:

189683

AN:

247858

AF XY:

0.774

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 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

AC:

10421

AN:

33398

Gnomad4 AMR exome

AF:

0.751

AC:

33378

AN:

44436

Gnomad4 ASJ exome

AF:

0.790

AC:

20459

AN:

25898

Gnomad4 EAS exome

AF:

0.621

AC:

24629

AN:

39648

Gnomad4 SAS exome

AF:

0.732

AC:

62977

AN:

86034

Gnomad4 FIN exome

AF:

0.871

AC:

46411

AN:

53268

Gnomad4 NFE exome

AF:

0.836

AC:

928044

AN:

1109958

Gnomad4 Remaining exome

AF:

0.777

AC:

46775

AN:

60236

Heterozygous variant carriers

12755

25511

38266

51022

63777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

20866

41732

62598

83464

104330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AC:

0.337373

AN:

0.337373

Gnomad4 AMR

AF:

0.761

AC:

0.760599

AN:

0.760599

Gnomad4 ASJ

AF:

0.780

AC:

0.780403

AN:

0.780403

Gnomad4 EAS

AF:

0.645

AC:

0.644767

AN:

0.644767

Gnomad4 SAS

AF:

0.713

AC:

0.712978

AN:

0.712978

Gnomad4 FIN

AF:

0.880

AC:

0.879974

AN:

0.879974

Gnomad4 NFE

AF:

0.840

AC:

0.839996

AN:

0.839996

Gnomad4 OTH

AF:

0.711

AC:

0.710626

AN:

0.710626

Heterozygous variant carriers

1313

2626

3940

5253

6566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.792

Hom.:

205381

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

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

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