2-27079063-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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 (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: EMILIN1 NM_007046.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.305

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 -10 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 criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 375 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMILIN1	NM_007046.4	c.-3G>A		5_prime_UTR_variant	1/8	ENST00000380320.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMILIN1	ENST00000380320.9	c.-3G>A		5_prime_UTR_variant	1/8	1	NM_007046.4	P1

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 375 AN: 152152 Hom.: 0 Cov.: 32

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: 92 AN: 182132 Hom.: 0 AF XY: 0.000318 AC XY: 33 AN XY: 103672

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.: 0 Cov.: 31 AF XY: 0.000189 AC XY: 132 AN XY: 697844

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.: 0 Cov.: 32 AF XY: 0.00211 AC XY: 157 AN XY: 74440

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.: 0

Bravo AF: 0.00280

Asia WGS AF: 0.000866 AC: 3 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

Dec 06, 2019

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

Other links and lift over

dbSNP: rs202187885; hg19: chr2-27301931; COSMIC: COSV66694455; COSMIC: COSV66694455;