2-27080194-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007046.4(EMILIN1):c.214C>G(p.Leu72Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,614,064 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0093 (22 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (28 hom.)
• Consequence: EMILIN1 NM_007046.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.07

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007603556).
• BP6: Variant 2-27080194-C-G is Benign according to our data. Variant chr2-27080194-C-G is described in ClinVar as [Benign]. Clinvar id is 3057164.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00925 (1409/152278) while in subpopulation AFR AF= 0.0323 (1341/41550). AF 95% confidence interval is 0.0308. There are 22 homozygotes in gnomad4. There are 670 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1404 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMILIN1	NM_007046.4	c.214C>G	p.Leu72Val	missense_variant	2/8	ENST00000380320.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMILIN1	ENST00000380320.9	c.214C>G	p.Leu72Val	missense_variant	2/8	1	NM_007046.4	P1

Frequencies

GnomAD3 genomes AF: 0.00923 AC: 1404 AN: 152160 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00232 AC: 584 AN: 251356 Hom.: 5 AF XY: 0.00154 AC XY: 209 AN XY: 135866

Gnomad AFR exome AF: 0.0329

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00104 AC: 1524 AN: 1461786 Hom.: 28 Cov.: 31 AF XY: 0.000928 AC XY: 675 AN XY: 727204

Gnomad4 AFR exome AF: 0.0360

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000809

Gnomad4 OTH exome AF: 0.00243

GnomAD4 genome AF: 0.00925 AC: 1409 AN: 152278 Hom.: 22 Cov.: 33 AF XY: 0.00900 AC XY: 670 AN XY: 74460

Gnomad4 AFR AF: 0.0323

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00141 Hom.: 1

Bravo AF: 0.0109

ESP6500AA AF: 0.0340 AC: 150

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00320 AC: 388

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

EMILIN1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 07, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	19
Dann	Benign	0.35
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.017
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N
MutationTaster	Benign	0.89	D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.11
Sift	Benign	0.89	T
Sift4G	Benign	1.0	T
Polyphen		0.45	B
Vest4		0.26
MVP		0.28
MPC		0.40
ClinPred		0.024	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.18
gMVP		0.28

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

Other links and lift over

dbSNP: rs75246647; hg19: chr2-27303062;