rs55951999

Variant names:

• chr7-74035400-G-A
• NM_000501.4:c.119G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-74035400-G-A
• chr7-74035400-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000501.4(ELN):​c.119G>A​(p.Gly40Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ELN NM_000501.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12

Genes affected

ELN (HGNC:3327): (elastin) This gene encodes a protein that is one of the two components of elastic fibers. Elastic fibers comprise part of the extracellular matrix and confer elasticity to organs and tissues including the heart, skin, lungs, ligaments, and blood vessels. The encoded protein is rich in hydrophobic amino acids such as glycine and proline, which form mobile hydrophobic regions bounded by crosslinks between lysine residues. Degradation products of the encoded protein, known as elastin-derived peptides or elastokines, bind the elastin receptor complex and other receptors and stimulate migration and proliferation of monocytes and skin fibroblasts. Elastokines can also contribute to cancer progression. Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVAS) and autosomal dominant cutis laxa. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
ELN	NM_000501.4	c.119G>A	p.Gly40Glu	missense_variant	Exon 2 of 33	ENST00000252034.12	NP_000492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12	c.119G>A	p.Gly40Glu	missense_variant	Exon 2 of 33	1	NM_000501.4	ENSP00000252034.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T;.;T;T;T;.;T;.;.;.;.;T;.;.;.;.;.;.;T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D;T;D;D;D;T;D;D;T;D;T;D;D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.9	.;.;L;L;.;.;.;.;.;L;L;L;.;L;.;L;.;L;L;.;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.1	N;.;N;N;D;N;D;D;N;N;D;N;N;N;D;D;D;N;D;D;N
REVEL	Uncertain	0.50
Sift	Pathogenic	0.0	D;.;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;.;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.87	P;P;P;.;.;P;.;.;P;P;P;P;P;P;.;P;.;P;P;.;.
Vest4		0.75
MutPred		0.41		Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);Loss of catalytic residue at V41 (P = 0.0849);
MVP		0.86
MPC		0.24
ClinPred		0.73	D
GERP RS		3.1
Varity_R		0.097
gMVP		0.70

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-73449730; COSMIC: COSV52715364;