18-2900030-C-T

Variant names:

• chr18-2900030-C-T
• rs11080995
• NM_032048.3:c.2360-6753C>T

Variant summary

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

The NM_032048.3(EMILIN2):​c.2360-6753C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,096 control chromosomes in the GnomAD database, including 45,459 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 0.77 (45459 hom., cov: 32)
• Consequence: EMILIN2 NM_032048.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 0 publications found

Genes affected

EMILIN2 (HGNC:19881): (elastin microfibril interfacer 2) Predicted to enable extracellular matrix constituent conferring elasticity. Predicted to be involved in cell adhesion. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LPIN2 (HGNC:14450): (lipin 2) Mouse studies suggest that this gene functions during normal adipose tissue development and may play a role in human triglyceride metabolism. This gene represents a candidate gene for human lipodystrophy, characterized by loss of body fat, fatty liver, hypertriglyceridemia, and insulin resistance. [provided by RefSeq, Jul 2008]

LPIN2 Gene-Disease associations (from GenCC):

• Majeed syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032048.3. 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
	EMILIN2	NM_032048.3	MANE Select	c.2360-6753C>T		intron	N/A	NP_114437.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMILIN2	ENST00000254528.4	TSL:1 MANE Select	c.2360-6753C>T		intron	N/A	ENSP00000254528.3
	EMILIN2	ENST00000942047.1		c.2360-6753C>T		intron	N/A	ENSP00000612106.1
	EMILIN2	ENST00000942046.1		c.2237-6753C>T		intron	N/A	ENSP00000612105.1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117443 AN: 151978 Hom.: 45406 Cov.: 32

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.773 AC: 117549 AN: 152096 Hom.: 45459 Cov.: 32 AF XY: 0.776 AC XY: 57682 AN XY: 74344

African (AFR) AF: 0.774 AC: 32091 AN: 41472

American (AMR) AF: 0.822 AC: 12567 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2614 AN: 3472

East Asian (EAS) AF: 0.858 AC: 4438 AN: 5174

South Asian (SAS) AF: 0.810 AC: 3910 AN: 4828

European-Finnish (FIN) AF: 0.765 AC: 8082 AN: 10568

Middle Eastern (MID) AF: 0.769 AC: 223 AN: 290

European-Non Finnish (NFE) AF: 0.755 AC: 51319 AN: 67980

Other (OTH) AF: 0.784 AC: 1652 AN: 2106

Alfa AF: 0.763 Hom.: 99027

Bravo AF: 0.778

Asia WGS AF: 0.857 AC: 2983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.018
DANN	Benign	0.70
PhyloP100		-1.5
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: rs11080995; hg19: chr18-2900028;