2-27079210-GC-G

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_007046.4(EMILIN1):c.151del(p.Arg51GlyfsTer14) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000422 in 1,422,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: EMILIN1 NM_007046.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.235

Genes affected

EMILIN1 (HGNC:19880): (elastin microfibril interfacer 1) This gene encodes an extracellular matrix glycoprotein that is characterized by an N-terminal microfibril interface domain, a coiled-coiled alpha-helical domain, a collagenous domain and a C-terminal globular C1q domain. The encoded protein associates with elastic fibers at the interface between elastin and microfibrils and may play a role in the development of elastic tissues including large blood vessels, dermis, heart and lung. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 2-27079210-GC-G is Pathogenic according to our data. Variant chr2-27079210-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 1527981.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-27079210-GC-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMILIN1	NM_007046.4	c.151del	p.Arg51GlyfsTer14	frameshift_variant	1/8	ENST00000380320.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMILIN1	ENST00000380320.9	c.151del	p.Arg51GlyfsTer14	frameshift_variant	1/8	1	NM_007046.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000422 AC: 6 AN: 1422734 Hom.: 0 Cov.: 31 AF XY: 0.00000706 AC XY: 5 AN XY: 708132

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000287

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000363

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Arterial tortuosity Pathogenic:1

Pathogenic, no assertion criteria provided

research

Center for Medical Genetics Ghent, University of Ghent

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Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27302078;