8-24472122-CAAAAAAAA-CAAAAA

Variant names:

• chr8-24472122-CAAA-C
• rs55708871
• NM_003817.4:c.633+3316_633+3318delAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003817.4(ADAM7):​c.633+3316_633+3318delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 102,754 control chromosomes in the GnomAD database, including 98 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.029 (98 hom., cov: 23)
• Consequence: ADAM7 NM_003817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682
• Publications: 0 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-AS1 (HGNC:56152): (ADAM7, ADAMDEC1 and ADAM28 antisense RNA 1)

ACMG classification

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

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003817.4. 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
	ADAM7	NM_003817.4	MANE Select	c.633+3316_633+3318delAAA		intron	N/A	NP_003808.2	A0A384MTL6
	ADAM7-AS1	NR_125808.1		n.79+76415_79+76417delTTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM7	ENST00000175238.10	TSL:1 MANE Select	c.633+3303_633+3305delAAA		intron	N/A	ENSP00000175238.5	Q9H2U9-1
	ADAM7	ENST00000380789.5	TSL:5	c.633+3303_633+3305delAAA		intron	N/A	ENSP00000370166.1	C9JK28
	ADAM7-AS1	ENST00000519689.1	TSL:4	n.185-84134_185-84132delTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 2979 AN: 102762 Hom.: 98 Cov.: 23

Gnomad AFR AF: 0.0933

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.0180

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

GnomAD4 genome AF: 0.0290 AC: 2977 AN: 102754 Hom.: 98 Cov.: 23 AF XY: 0.0286 AC XY: 1404 AN XY: 49010

African (AFR) AF: 0.0932 AC: 2841 AN: 30498

American (AMR) AF: 0.0101 AC: 95 AN: 9432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2458

East Asian (EAS) AF: 0.00 AC: 0 AN: 3714

South Asian (SAS) AF: 0.000700 AC: 2 AN: 2858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 178

European-Non Finnish (NFE) AF: 0.000280 AC: 13 AN: 46414

Other (OTH) AF: 0.0179 AC: 26 AN: 1452

Alfa AF: 0.00 Hom.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.68

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: rs55708871; hg19: chr8-24329635;