rs2304682

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-27084901-G-A
• chr2-27084901-G-C
• chr2-27084901-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_007046.4(EMILIN1):​c.2558-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000447 in 1,119,414 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000045 (0 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):

• 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)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High AC in GnomAdExome4 at 5 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.2558-90G>A		intron	N/A	NP_008977.1	Q9Y6C2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMILIN1	ENST00000380320.9	TSL:1 MANE Select	c.2558-90G>A		intron	N/A	ENSP00000369677.4	Q9Y6C2-1
	EMILIN1	ENST00000957377.1		c.2843-90G>A		intron	N/A	ENSP00000627436.1
	EMILIN1	ENST00000957375.1		c.2843-90G>A		intron	N/A	ENSP00000627434.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000447 AC: 5 AN: 1119414 Hom.: 0 AF XY: 0.00000524 AC XY: 3 AN XY: 572352

African (AFR) AF: 0.00 AC: 0 AN: 26788

American (AMR) AF: 0.00 AC: 0 AN: 44144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23990

East Asian (EAS) AF: 0.00 AC: 0 AN: 38050

South Asian (SAS) AF: 0.00 AC: 0 AN: 79580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5086

European-Non Finnish (NFE) AF: 0.00000500 AC: 4 AN: 799840

Other (OTH) AF: 0.0000203 AC: 1 AN: 49178

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1577

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.92
PhyloP100		-0.26

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;