chr7-74028118-G-T

Variant names:

• chr7-74028118-G-T
• rs537200597
• ENST00000869840.1:c.-70G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000445912.5(ELN):​c.-70G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 569,666 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 0.00022 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: ELN ENST00000445912.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.927
• Publications: 0 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, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• supravalvular aortic stenosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000222 (26/117110) while in subpopulation AFR AF = 0.000681 (21/30842). AF 95% confidence interval is 0.000456. There are 0 homozygotes in GnomAd4. There are 11 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 26 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000445912.5. 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.-70G>T		upstream_gene	N/A	NP_000492.2	P15502-2
	ELN	NM_001278939.2		c.-70G>T		upstream_gene	N/A	NP_001265868.1	P15502-3
	ELN	NM_001278915.2		c.-70G>T		upstream_gene	N/A	NP_001265844.1	P15502-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	ENST00000869840.1		c.-70G>T		5_prime_UTR	Exon 1 of 33	ENSP00000539899.1
	ELN	ENST00000869804.1		c.-70G>T		5_prime_UTR	Exon 1 of 33	ENSP00000539863.1
	ELN	ENST00000869842.1		c.-70G>T		5_prime_UTR	Exon 1 of 33	ENSP00000539901.1

Frequencies

GnomAD3 genomes AF: 0.000222 AC: 26 AN: 117040 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000682

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000504

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000312 AC: 141 AN: 452556 Hom.: 0 Cov.: 15 AF XY: 0.000314 AC XY: 73 AN XY: 232844

African (AFR) AF: 0.00195 AC: 23 AN: 11824

American (AMR) AF: 0.00 AC: 0 AN: 26528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10158

East Asian (EAS) AF: 0.00 AC: 0 AN: 9510

South Asian (SAS) AF: 0.0000199 AC: 1 AN: 50330

European-Finnish (FIN) AF: 0.0000492 AC: 1 AN: 20344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2692

European-Non Finnish (NFE) AF: 0.000368 AC: 112 AN: 304150

Other (OTH) AF: 0.000235 AC: 4 AN: 17020

GnomAD4 genome AF: 0.000222 AC: 26 AN: 117110 Hom.: 0 Cov.: 29 AF XY: 0.000203 AC XY: 11 AN XY: 54320

African (AFR) AF: 0.000681 AC: 21 AN: 30842

American (AMR) AF: 0.000210 AC: 2 AN: 9524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3148

East Asian (EAS) AF: 0.00 AC: 0 AN: 3378

South Asian (SAS) AF: 0.00 AC: 0 AN: 3172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 180

European-Non Finnish (NFE) AF: 0.0000504 AC: 3 AN: 59532

Other (OTH) AF: 0.00 AC: 0 AN: 1564

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	16
DANN	Benign	0.88
PhyloP100		0.93
PromoterAI		-0.044	Neutral

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: rs537200597; hg19: chr7-73442448;