rs798544

chr7-2723468-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000489665.1(AMZ1):n.550+13652C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,188 control chromosomes in the GnomAD database, including 5,251 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 0.25 (5251 hom., cov: 33)
• Consequence: AMZ1 ENST00000489665.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513

Genes affected

AMZ1 (HGNC:22231): (archaelysin family metallopeptidase 1) Predicted to enable metal ion binding activity and metallopeptidase activity. Predicted to be involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMZ1	NM_001321766.2	c.948+13652C>T		intron_variant
AMZ1	NM_001384740.1	c.948+13652C>T		intron_variant
AMZ1	NM_001384741.1	c.779-7553C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMZ1	ENST00000489665.1	n.550+13652C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38045 AN: 152070 Hom.: 5249 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.250 AC: 38058 AN: 152188 Hom.: 5251 Cov.: 33 AF XY: 0.253 AC XY: 18787 AN XY: 74398

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.254

Alfa AF: 0.280 Hom.: 14430

Bravo AF: 0.240

Asia WGS AF: 0.236 AC: 823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.0
Dann	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs798544; hg19: chr7-2763102; COSMIC: COSV51738339;