7-74037810-G-A

Variant names:

• chr7-74037810-G-A
• rs2301995
• NM_000501.4:c.196+71G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001278939.2(ELN):​c.196+71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 1,578,610 control chromosomes in the GnomAD database, including 6,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1333 hom., cov: 32)
  • Exomes 𝑓: 0.073 (4834 hom.)
• Consequence: ELN NM_001278939.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.144
• Publications: 26 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, Genomics England PanelApp, G2P
• supravalvular aortic stenosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-74037810-G-A is Benign according to our data. Variant chr7-74037810-G-A is described in ClinVar as Benign. ClinVar VariationId is 1297183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278939.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	NM_000501.4	MANE Select	c.196+71G>A		intron	N/A	NP_000492.2
	ELN	NM_001278939.2		c.196+71G>A		intron	N/A	NP_001265868.1
	ELN	NM_001278915.2		c.196+71G>A		intron	N/A	NP_001265844.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	ENST00000252034.12	TSL:1 MANE Select	c.196+71G>A		intron	N/A	ENSP00000252034.7
	ELN	ENST00000380562.8	TSL:1	c.196+71G>A		intron	N/A	ENSP00000369936.4
	ELN	ENST00000458204.5	TSL:1	c.166+71G>A		intron	N/A	ENSP00000403162.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17141 AN: 152064 Hom.: 1328 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0966

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0563

Gnomad OTH AF: 0.0940

GnomAD4 exome AF: 0.0734 AC: 104631 AN: 1426428 Hom.: 4834 Cov.: 28 AF XY: 0.0736 AC XY: 52015 AN XY: 706824

African (AFR) AF: 0.220 AC: 7280 AN: 33054

American (AMR) AF: 0.123 AC: 4770 AN: 38736

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 812 AN: 25362

East Asian (EAS) AF: 0.208 AC: 8049 AN: 38774

South Asian (SAS) AF: 0.112 AC: 9169 AN: 82122

European-Finnish (FIN) AF: 0.0863 AC: 4399 AN: 50990

Middle Eastern (MID) AF: 0.0710 AC: 405 AN: 5704

European-Non Finnish (NFE) AF: 0.0592 AC: 64735 AN: 1092582

Other (OTH) AF: 0.0848 AC: 5012 AN: 59104

GnomAD4 genome AF: 0.113 AC: 17156 AN: 152182 Hom.: 1333 Cov.: 32 AF XY: 0.115 AC XY: 8588 AN XY: 74418

African (AFR) AF: 0.207 AC: 8605 AN: 41498

American (AMR) AF: 0.108 AC: 1656 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1087 AN: 5164

South Asian (SAS) AF: 0.122 AC: 587 AN: 4820

European-Finnish (FIN) AF: 0.0966 AC: 1026 AN: 10616

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0563 AC: 3829 AN: 68012

Other (OTH) AF: 0.0939 AC: 198 AN: 2108

Alfa AF: 0.0770 Hom.: 340

Bravo AF: 0.119

Asia WGS AF: 0.174 AC: 602 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.50
PhyloP100		-0.14
PromoterAI		0.075	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs2301995; hg19: chr7-73452140; COSMIC: COSV52706883; COSMIC: COSV52706883;