rs2011616

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
EMILIN1	NM_007046.4	c.170+458G>A		intron_variant		ENST00000380320.9	NP_008977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMILIN1	ENST00000380320.9	c.170+458G>A		intron_variant		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

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.395

Alfa AF: 0.407 Hom.: 15530

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2011616; hg19: chr2-27302561;