2-27079297-T-C

Variant names:

• chr2-27079297-T-C
• rs2289360
• NM_007046.4:c.170+62T>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.170+62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,371,956 control chromosomes in the GnomAD database, including 265,064 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 0.56 (24686 hom., cov: 33)
  • Exomes 𝑓: 0.62 (240378 hom.)
• Consequence: EMILIN1 NM_007046.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.64
• Publications: 19 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

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.170+62T>C		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.170+62T>C		intron	N/A	ENSP00000369677.4	Q9Y6C2-1
	EMILIN1	ENST00000957377.1		c.170+62T>C		intron	N/A	ENSP00000627436.1
	EMILIN1	ENST00000957375.1		c.170+62T>C		intron	N/A	ENSP00000627434.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85121 AN: 152004 Hom.: 24672 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.576

GnomAD4 exome AF: 0.624 AC: 761618 AN: 1219834 Hom.: 240378 AF XY: 0.626 AC XY: 378186 AN XY: 604208

African (AFR) AF: 0.425 AC: 10164 AN: 23904

American (AMR) AF: 0.403 AC: 7994 AN: 19860

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 12644 AN: 21034

East Asian (EAS) AF: 0.783 AC: 23505 AN: 30002

South Asian (SAS) AF: 0.681 AC: 47181 AN: 69252

European-Finnish (FIN) AF: 0.651 AC: 31122 AN: 47796

Middle Eastern (MID) AF: 0.621 AC: 3186 AN: 5134

European-Non Finnish (NFE) AF: 0.624 AC: 594265 AN: 951902

Other (OTH) AF: 0.619 AC: 31557 AN: 50950

GnomAD4 genome AF: 0.560 AC: 85150 AN: 152122 Hom.: 24686 Cov.: 33 AF XY: 0.562 AC XY: 41804 AN XY: 74382

African (AFR) AF: 0.432 AC: 17948 AN: 41518

American (AMR) AF: 0.457 AC: 6992 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2088 AN: 3468

East Asian (EAS) AF: 0.771 AC: 3979 AN: 5160

South Asian (SAS) AF: 0.690 AC: 3330 AN: 4824

European-Finnish (FIN) AF: 0.659 AC: 6989 AN: 10604

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 41999 AN: 67942

Other (OTH) AF: 0.573 AC: 1208 AN: 2110

Alfa AF: 0.568 Hom.: 3580

Bravo AF: 0.534

Asia WGS AF: 0.682 AC: 2372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.019
DANN	Benign	0.45
PhyloP100		-4.6
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: rs2289360; hg19: chr2-27302165;