Genetic Variant EMILIN1:c.-3G>A (chr2-27079063-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_007046.4(EMILIN1):c.-3G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000459 in 1,555,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

EMILIN1
NM_007046.4 5_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.305

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 2-27079063-G-A is Benign according to our data. Variant chr2-27079063-G-A is described in ClinVar as [Benign]. Clinvar id is 3048837.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00246 (375/152268) while in subpopulation AFR AF= 0.00878 (365/41564). AF 95% confidence interval is 0.00804. There are 0 homozygotes in gnomad4. There are 157 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 375 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMILIN1	NM_007046.4 link	c.-3G>A		5_prime_UTR_variant	Exon 1 of 8	ENST00000380320.9	NP_008977.1	Q9Y6C2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMILIN1	ENST00000380320 link	c.-3G>A		5_prime_UTR_variant	Exon 1 of 8	1	NM_007046.4	ENSP00000369677.4		Q9Y6C2-1

Frequencies

GnomAD3 genomes

AF:

0.00246

AC:

375

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00881

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000505

AC:

AN:

182132

Hom.:

AF XY:

0.000318

AC XY:

AN XY:

103672

show subpopulations

Gnomad AFR exome

AF:

0.00782

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000929

Gnomad SAS exome

AF:

0.0000395

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000241

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000242

AC:

339

AN:

1403658

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

132

AN XY:

697844

show subpopulations

Gnomad4 AFR exome

AF:

0.00829

Gnomad4 AMR exome

AF:

0.000475

Gnomad4 ASJ exome

AF:

0.0000427

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000617

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000367

Gnomad4 OTH exome

AF:

0.000521

GnomAD4 genome

AF:

0.00246

AC:

375

AN:

152268

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

157

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00878

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.00280

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EMILIN1-related disorder

Benign:1

Dec 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.9

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over