chr1-203348034-C-T

Variant names:

• chr1-203348034-C-T
• rs7543148
• NM_002023.5:c.237G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (39237 hom., cov: 31)
  • Exomes 𝑓: 0.81 (481416 hom.)
• Consequence: FMOD NM_002023.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.028).
• 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	c.237G>A	p.Glu79Glu	synonymous_variant	Exon 2 of 3	ENST00000354955.5	NP_002014.2
FMOD	XM_047416304.1	c.237G>A	p.Glu79Glu	synonymous_variant	Exon 3 of 4		XP_047272260.1
FMOD	NR_103757.2	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	c.237G>A	p.Glu79Glu	synonymous_variant	Exon 2 of 3	1	NM_002023.5	ENSP00000347041.4

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103911 AN: 151936 Hom.: 39239 Cov.: 31

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

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.: 67 AF XY: 0.807 AC XY: 585013 AN XY: 725220

African (AFR) AF: 0.312 AC: 10421 AN: 33398

American (AMR) AF: 0.751 AC: 33378 AN: 44436

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 20459 AN: 25898

East Asian (EAS) AF: 0.621 AC: 24629 AN: 39648

South Asian (SAS) AF: 0.732 AC: 62977 AN: 86034

European-Finnish (FIN) AF: 0.871 AC: 46411 AN: 53268

Middle Eastern (MID) AF: 0.742 AC: 4272 AN: 5754

European-Non Finnish (NFE) AF: 0.836 AC: 928044 AN: 1109958

Other (OTH) AF: 0.777 AC: 46775 AN: 60236

GnomAD4 genome AF: 0.684 AC: 103936 AN: 152054 Hom.: 39237 Cov.: 31 AF XY: 0.688 AC XY: 51170 AN XY: 74342

African (AFR) AF: 0.337 AC: 13976 AN: 41426

American (AMR) AF: 0.761 AC: 11625 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2708 AN: 3470

East Asian (EAS) AF: 0.645 AC: 3327 AN: 5160

South Asian (SAS) AF: 0.713 AC: 3428 AN: 4808

European-Finnish (FIN) AF: 0.880 AC: 9333 AN: 10606

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57108 AN: 67986

Other (OTH) AF: 0.711 AC: 1498 AN: 2108

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
PhyloP100		0.58
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

Other links and lift over

dbSNP: rs7543148; hg19: chr1-203317162; COSMIC: COSV61609680;