7-74059938-C-T

Variant names:

• chr7-74059938-C-T
• rs200512332
• NM_000501.4:c.1467C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000501.4(ELN):​c.1467C>T​(p.Val489Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000816 in 1,592,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000071 (0 hom.)
• Consequence: ELN NM_000501.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.49
• Publications: 1 publications found

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]

ELN-AS1 (HGNC:40212): (ELN antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-74059938-C-T is Benign according to our data. Variant chr7-74059938-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 908281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.49 with no splicing effect.
• BS2: High AC in GnomAd4 at 27 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000501.4. 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
	ELN	NM_000501.4	MANE Select	c.1467C>T	p.Val489Val	synonymous	Exon 23 of 33	NP_000492.2	P15502-2
	ELN	NM_001278939.2		c.1554C>T	p.Val518Val	synonymous	Exon 24 of 34	NP_001265868.1	P15502-3
	ELN	NM_001278915.2		c.1485C>T	p.Val495Val	synonymous	Exon 23 of 33	NP_001265844.1	P15502-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	ENST00000252034.12	TSL:1 MANE Select	c.1467C>T	p.Val489Val	synonymous	Exon 23 of 33	ENSP00000252034.7	P15502-2
	ELN	ENST00000380562.8	TSL:1	c.1485C>T	p.Val495Val	synonymous	Exon 23 of 33	ENSP00000369936.4	P15502-1
	ELN	ENST00000458204.5	TSL:1	c.1437C>T	p.Val479Val	synonymous	Exon 22 of 32	ENSP00000403162.1	E7EN65

Frequencies

GnomAD3 genomes AF: 0.000180 AC: 27 AN: 150154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00265

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000852

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000445

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000151 AC: 38 AN: 251456 AF XY: 0.000140

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000714 AC: 103 AN: 1442696 Hom.: 0 Cov.: 28 AF XY: 0.0000696 AC XY: 50 AN XY: 718708

African (AFR) AF: 0.000242 AC: 8 AN: 33098

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00252 AC: 65 AN: 25762

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39614

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.0000110 AC: 12 AN: 1094876

Other (OTH) AF: 0.000117 AC: 7 AN: 59738

GnomAD4 genome AF: 0.000180 AC: 27 AN: 150154 Hom.: 0 Cov.: 32 AF XY: 0.000232 AC XY: 17 AN XY: 73276

African (AFR) AF: 0.000270 AC: 11 AN: 40754

American (AMR) AF: 0.00 AC: 0 AN: 15088

Ashkenazi Jewish (ASJ) AF: 0.00265 AC: 9 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 5102

South Asian (SAS) AF: 0.000852 AC: 4 AN: 4694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000445 AC: 3 AN: 67404

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.000302 Hom.: 0

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Supravalvar aortic stenosis (2)
-	-	1	Cutis laxa, autosomal dominant 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.69
PhyloP100		-2.5
Mutation Taster		=99/1	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: rs200512332; hg19: chr7-73474268; COSMIC: COSV52709218; COSMIC: COSV52709218;