rs798470

Variant names:

• chr7-2702463-T-C
• rs798470
• NM_001384743.1:c.305-259T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-2702463-T-C
• chr7-2702463-T-G

Variant summary

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

The NM_001384743.1(AMZ1):​c.305-259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 490,732 control chromosomes in the GnomAD database, including 92,353 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 0.66 (35444 hom., cov: 34)
  • Exomes 𝑓: 0.57 (56909 hom.)
• Consequence: AMZ1 NM_001384743.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMZ1	NM_001384743.1	c.305-259T>C		intron_variant	Intron 2 of 6	ENST00000683327.1	NP_001371672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMZ1	ENST00000683327.1	c.305-259T>C		intron_variant	Intron 2 of 6		NM_001384743.1	ENSP00000506962.1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 101041 AN: 152088 Hom.: 35372 Cov.: 34

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.648

GnomAD4 exome AF: 0.569 AC: 192768 AN: 338526 Hom.: 56909 Cov.: 3 AF XY: 0.563 AC XY: 98497 AN XY: 174800

African (AFR) AF: 0.893 AC: 7464 AN: 8354

American (AMR) AF: 0.546 AC: 5582 AN: 10230

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 5647 AN: 11366

East Asian (EAS) AF: 0.333 AC: 7543 AN: 22674

South Asian (SAS) AF: 0.464 AC: 11731 AN: 25260

European-Finnish (FIN) AF: 0.672 AC: 16999 AN: 25298

Middle Eastern (MID) AF: 0.470 AC: 794 AN: 1688

European-Non Finnish (NFE) AF: 0.587 AC: 124773 AN: 212598

Other (OTH) AF: 0.581 AC: 12235 AN: 21058

GnomAD4 genome AF: 0.665 AC: 101173 AN: 152206 Hom.: 35444 Cov.: 34 AF XY: 0.661 AC XY: 49171 AN XY: 74406

African (AFR) AF: 0.896 AC: 37219 AN: 41554

American (AMR) AF: 0.569 AC: 8712 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1735 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1588 AN: 5174

South Asian (SAS) AF: 0.467 AC: 2253 AN: 4824

European-Finnish (FIN) AF: 0.685 AC: 7257 AN: 10598

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40333 AN: 67970

Other (OTH) AF: 0.651 AC: 1377 AN: 2114

Alfa AF: 0.691 Hom.: 17079

Bravo AF: 0.666

Asia WGS AF: 0.495 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.60
PhyloP100		-1.6
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: rs798470; hg19: chr7-2742097; COSMIC: COSV56689180; COSMIC: COSV56689180;