7-74069359-G-T

Variant names:

• chr7-74069359-G-T
• rs8326
• NM_000501.4:c.*659G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000501.4(ELN):​c.*659G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000846 in 236,408 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000071 (0 hom.)
• Consequence: ELN NM_000501.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• Publications: 11 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 Gene-Disease associations (from GenCC):

• cutis laxa, autosomal dominant 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• supravalvular aortic stenosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• autosomal dominant cutis laxa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High AC in GnomAd4 at 14 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.*659G>T		3_prime_UTR	Exon 33 of 33	NP_000492.2	P15502-2
	ELN	NM_001278939.2		c.*659G>T		3_prime_UTR	Exon 34 of 34	NP_001265868.1	P15502-3
	ELN	NM_001278915.2		c.*659G>T		3_prime_UTR	Exon 33 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.*659G>T		3_prime_UTR	Exon 33 of 33	ENSP00000252034.7	P15502-2
	ELN	ENST00000458204.5	TSL:1	c.*659G>T		3_prime_UTR	Exon 32 of 32	ENSP00000403162.1	E7EN65
	ELN	ENST00000357036.9	TSL:1	c.*659G>T		3_prime_UTR	Exon 32 of 32	ENSP00000349540.5	P15502-5

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 151984 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000712 AC: 6 AN: 84306 Hom.: 0 Cov.: 0 AF XY: 0.0000769 AC XY: 3 AN XY: 39002

African (AFR) AF: 0.00 AC: 0 AN: 3906

American (AMR) AF: 0.00 AC: 0 AN: 3104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5144

East Asian (EAS) AF: 0.00 AC: 0 AN: 11440

South Asian (SAS) AF: 0.00 AC: 0 AN: 910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 646

Middle Eastern (MID) AF: 0.00202 AC: 1 AN: 496

European-Non Finnish (NFE) AF: 0.0000966 AC: 5 AN: 51738

Other (OTH) AF: 0.00 AC: 0 AN: 6922

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152102 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74352

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.000327 AC: 5 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 619

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.80
DANN	Benign	0.70
PhyloP100		-0.66

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: rs8326; hg19: chr7-73483689;