chr2-27084901-G-C

Variant names:

• chr2-27084901-G-C
• rs2304682
• NM_007046.4:c.2558-90G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007046.4(EMILIN1):​c.2558-90G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 1,269,510 control chromosomes in the GnomAD database, including 261,222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (33035 hom., cov: 33)
  • Exomes 𝑓: 0.64 (228187 hom.)
• Consequence: EMILIN1 NM_007046.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• Publications: 14 publications found

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):

• neuronopathy, distal hereditary motor, autosomal dominant 10

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMILIN1	NM_007046.4	c.2558-90G>C		intron_variant	Intron 5 of 7	ENST00000380320.9	NP_008977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMILIN1	ENST00000380320.9	c.2558-90G>C		intron_variant	Intron 5 of 7	1	NM_007046.4	ENSP00000369677.4
EMILIN1	ENST00000433140.1	c.548-90G>C		intron_variant	Intron 2 of 4	2		ENSP00000411201.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99328 AN: 152030 Hom.: 33008 Cov.: 33

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.642

GnomAD4 exome AF: 0.635 AC: 710018 AN: 1117362 Hom.: 228187 AF XY: 0.637 AC XY: 363791 AN XY: 571358

African (AFR) AF: 0.740 AC: 19803 AN: 26758

American (AMR) AF: 0.394 AC: 17399 AN: 44134

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 14653 AN: 23960

East Asian (EAS) AF: 0.788 AC: 29978 AN: 38042

South Asian (SAS) AF: 0.683 AC: 54327 AN: 79522

European-Finnish (FIN) AF: 0.656 AC: 34620 AN: 52738

Middle Eastern (MID) AF: 0.650 AC: 3303 AN: 5078

European-Non Finnish (NFE) AF: 0.632 AC: 504319 AN: 798008

Other (OTH) AF: 0.644 AC: 31616 AN: 49122

GnomAD4 genome AF: 0.653 AC: 99399 AN: 152148 Hom.: 33035 Cov.: 33 AF XY: 0.653 AC XY: 48541 AN XY: 74386

African (AFR) AF: 0.743 AC: 30817 AN: 41502

American (AMR) AF: 0.495 AC: 7575 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2118 AN: 3470

East Asian (EAS) AF: 0.766 AC: 3964 AN: 5176

South Asian (SAS) AF: 0.689 AC: 3326 AN: 4830

European-Finnish (FIN) AF: 0.662 AC: 7014 AN: 10592

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42608 AN: 67978

Other (OTH) AF: 0.639 AC: 1346 AN: 2108

Alfa AF: 0.528 Hom.: 1577

Bravo AF: 0.640

Asia WGS AF: 0.695 AC: 2416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.57
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2304682; hg19: chr2-27307769;