NM_007046.4:c.214C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0093 ( 22 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 28 hom. )

Consequence

EMILIN1
NM_007046.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.07

Publications

3 publications found

Variant links:

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]

EMILIN1 Gene-Disease associations (from GenCC):

arterial tortuosity-bone fragility syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
neuronopathy, distal hereditary motor, autosomal dominant 10
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

EMILIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 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 VariationId is 3057164.Status of the report is no_assertion_criteria_provided, 0 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1409 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007046.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMILIN1	NM_007046.4	MANE Select	c.214C>G	p.Leu72Val	missense	Exon 2 of 8	NP_008977.1	Q9Y6C2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMILIN1	ENST00000380320.9	TSL:1 MANE Select	c.214C>G	p.Leu72Val	missense	Exon 2 of 8	ENSP00000369677.4	Q9Y6C2-1
EMILIN1	ENST00000957377.1		c.214C>G	p.Leu72Val	missense	Exon 2 of 8	ENSP00000627436.1
EMILIN1	ENST00000957375.1		c.214C>G	p.Leu72Val	missense	Exon 2 of 7	ENSP00000627434.1

Frequencies

GnomAD3 genomes

AF:

0.00923

AC:

1404

AN:

152160

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00232

AC:

584

AN:

251356

AF XY:

0.00154

show subpopulations

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 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.:

Cov.:

AF XY:

0.000928

AC XY:

675

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0360

AC:

1204

AN:

33478

American (AMR)

AF:

0.00141

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000809

AC:

AN:

1111940

Other (OTH)

AF:

0.00243

AC:

147

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

143

215

286

358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.00925

AC:

1409

AN:

152278

Hom.:

Cov.:

AF XY:

0.00900

AC XY:

670

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0323

AC:

1341

AN:

41550

American (AMR)

AF:

0.00301

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68014

Other (OTH)

AF:

0.00803

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

136

203

271

339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00141

Hom.:

Bravo

AF:

0.0109

ESP6500AA

AF:

0.0340

AC:

150

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00320

AC:

388

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

EMILIN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.047

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.017

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0076

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

PhyloP100

2.1

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.33

REVEL

Benign

0.11

Sift

Benign

0.89

Sift4G

Benign

1.0

Polyphen

0.45

Vest4

0.26

MVP

0.28

MPC

0.40

ClinPred

0.024

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.18

gMVP

0.28

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over