Genetic Variant AMZ1:n.550+10345C>T (chr7-2720161-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001384740.1(AMZ1):c.948+10345C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,804 control chromosomes in the GnomAD database, including 5,247 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 ( 5247 hom., cov: 32)

Consequence

AMZ1
NM_001384740.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.272

Variant links:

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]

AMZ1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
AMZ1	NM_001384740.1 link	c.948+10345C>T	intron_variant	Intron 6 of 6	NP_001371669.1
AMZ1	NM_001321766.2 link	c.948+10345C>T	intron_variant	Intron 6 of 6	NP_001308695.1	Q400G9A4D202
AMZ1	NM_001384742.1 link	c.779-4320C>T	intron_variant	Intron 5 of 5	NP_001371671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMZ1	ENST00000489665.1 link	n.550+10345C>T		intron_variant	Intron 4 of 4	1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37852

AN:

151686

Hom.:

5245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.249

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

GnomAD4 genome

AF:

0.249

AC:

37863

AN:

151804

Hom.:

5247

Cov.:

AF XY:

0.252

AC XY:

18716

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.143

AC:

5926

AN:

41486

American (AMR)

AF:

0.284

AC:

4332

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

856

AN:

3466

East Asian (EAS)

AF:

0.218

AC:

1128

AN:

5172

South Asian (SAS)

AF:

0.155

AC:

749

AN:

4824

European-Finnish (FIN)

AF:

0.384

AC:

4061

AN:

10564

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.294

AC:

19925

AN:

67726

Other (OTH)

AF:

0.252

AC:

532

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1460

2920

4381

5841

7301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.273

Hom.:

9515

Bravo

AF:

0.238

Asia WGS

AF:

0.240

AC:

837

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.4

(source)

DANN

Benign

0.72

PhyloP100

-0.27

Splicing

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

Publications

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7-2720161-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over