rs2011616

Variant names:

• chr2-27079693-G-A
• rs2011616
• NM_007046.4:c.170+458G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-27079693-G-A
• chr2-27079693-G-T

Variant summary

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

The NM_007046.4(EMILIN1):​c.170+458G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,044 control chromosomes in the GnomAD database, including 10,899 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 0.37 (10899 hom., cov: 33)
• Consequence: EMILIN1 NM_007046.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• Publications: 22 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMILIN1	NM_007046.4	c.170+458G>A		intron_variant	Intron 1 of 7	ENST00000380320.9	NP_008977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMILIN1	ENST00000380320.9	c.170+458G>A		intron_variant	Intron 1 of 7	1	NM_007046.4	ENSP00000369677.4

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56124 AN: 151926 Hom.: 10876 Cov.: 33

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.392

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.370 AC: 56185 AN: 152044 Hom.: 10899 Cov.: 33 AF XY: 0.369 AC XY: 27426 AN XY: 74326

African (AFR) AF: 0.285 AC: 11831 AN: 41474

American (AMR) AF: 0.525 AC: 8017 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1461 AN: 3470

East Asian (EAS) AF: 0.233 AC: 1202 AN: 5156

South Asian (SAS) AF: 0.356 AC: 1717 AN: 4818

European-Finnish (FIN) AF: 0.327 AC: 3454 AN: 10576

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27041 AN: 67952

Other (OTH) AF: 0.395 AC: 835 AN: 2112

Alfa AF: 0.404 Hom.: 19492

Bravo AF: 0.385

Asia WGS AF: 0.316 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.79
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2011616; hg19: chr2-27302561;