2-27079228-C-T

Variant names:

• chr2-27079228-C-T
• rs758148332
• NM_007046.4:c.163C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007046.4(EMILIN1):​c.163C>T​(p.Arg55Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,410,802 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R55H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: EMILIN1 NM_007046.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• Publications: 2 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMILIN1	NM_007046.4	c.163C>T	p.Arg55Cys	missense_variant	Exon 1 of 8	ENST00000380320.9	NP_008977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMILIN1	ENST00000380320.9	c.163C>T	p.Arg55Cys	missense_variant	Exon 1 of 8	1	NM_007046.4	ENSP00000369677.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000543 AC: 1 AN: 184042 AF XY: 0.00000958

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000119

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1410802 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 702134

African (AFR) AF: 0.00 AC: 0 AN: 28692

American (AMR) AF: 0.00 AC: 0 AN: 33542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24150

East Asian (EAS) AF: 0.0000287 AC: 1 AN: 34806

South Asian (SAS) AF: 0.00 AC: 0 AN: 81340

European-Finnish (FIN) AF: 0.0000194 AC: 1 AN: 51480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1093216

Other (OTH) AF: 0.0000172 AC: 1 AN: 57986

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000167 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.51
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.44
MutPred		0.47		Loss of solvent accessibility (P = 8e-04);
MVP		0.88
MPC		0.52
ClinPred		0.88	D
GERP RS		3.9
Varity_R		0.14
gMVP		0.70
Mutation Taster		=78/22	polymorphism

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: rs758148332; hg19: chr2-27302096; COSMIC: COSV107500276; COSMIC: COSV107500276;