ENST00000520720.1:c.1525-5527G>A

Variant names:

• chr8-24521228-G-A
• rs11781622
• ENST00000520720.1:c.1525-5527G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520720.1(ADAM7):​c.1525-5527G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 150,648 control chromosomes in the GnomAD database, including 45,730 homozygotes. 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 0.77 (45730 hom., cov: 28)
• Consequence: ADAM7 ENST00000520720.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692
• Publications: 7 publications found

Genes affected

ADAM7 (HGNC:214): (ADAM metallopeptidase domain 7) This gene encodes a member of the ADAMs family of zinc proteases. These transmembrane proteins play roles in multiple processes including cell signaling, adhesion and migration. The encoded protein lacks protease activity and may play roles in protein-protein interactions and cell adhesion processes including sperm-egg fusion. Mutations in this gene may be involved in the progression of melanoma. [provided by RefSeq, Oct 2011]

ADAM7-AS2 (HGNC:56153): (ADAM7 antisense RNA 2)

ADAM7-AS1 (HGNC:56152): (ADAM7, ADAMDEC1 and ADAM28 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM7-AS1	NR_125808.1	n.79+27312C>T		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM7	ENST00000520720.1	c.1525-5527G>A		intron_variant	Intron 14 of 14	1		ENSP00000430400.1
ADAM7-AS2	ENST00000835533.1	n.198C>T		non_coding_transcript_exon_variant	Exon 2 of 2
ADAM7-AS1	ENST00000519689.1	n.185-133237C>T		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.769 AC: 115838 AN: 150554 Hom.: 45712 Cov.: 28

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.765

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.769 AC: 115897 AN: 150648 Hom.: 45730 Cov.: 28 AF XY: 0.775 AC XY: 56949 AN XY: 73518

African (AFR) AF: 0.576 AC: 23579 AN: 40952

American (AMR) AF: 0.807 AC: 12205 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2846 AN: 3472

East Asian (EAS) AF: 0.966 AC: 4959 AN: 5136

South Asian (SAS) AF: 0.874 AC: 4187 AN: 4792

European-Finnish (FIN) AF: 0.872 AC: 8848 AN: 10142

Middle Eastern (MID) AF: 0.776 AC: 225 AN: 290

European-Non Finnish (NFE) AF: 0.839 AC: 56820 AN: 67740

Other (OTH) AF: 0.767 AC: 1598 AN: 2084

Alfa AF: 0.816 Hom.: 150522

Bravo AF: 0.751

Asia WGS AF: 0.872 AC: 3007 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.7
DANN	Benign	0.38
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11781622; hg19: chr8-24378741;