dbSNP rs798470: AMZ1:c.305-259T>C (chr7-2702463-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58

Publications

1 publications found

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:

Genome browser will be placed here

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=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384743.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AMZ1	NM_001384743.1	MANE Select	c.305-259T>C	intron	N/A	NP_001371672.1
AMZ1	NM_133463.4		c.305-259T>C	intron	N/A	NP_597720.1
AMZ1	NM_001384739.1		c.305-259T>C	intron	N/A	NP_001371668.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AMZ1	ENST00000683327.1	MANE Select	c.305-259T>C	intron	N/A	ENSP00000506962.1
AMZ1	ENST00000312371.8	TSL:1	c.305-259T>C	intron	N/A	ENSP00000308149.4
AMZ1	ENST00000485540.5	TSL:1	n.424+19T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.664

AC:

101041

AN:

152088

Hom.:

35372

Cov.:

show subpopulations

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.:

AF XY:

0.563

AC XY:

98497

AN XY:

174800

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3655

7309

10964

14618

18273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

482

964

1446

1928

2410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.665

AC:

101173

AN:

152206

Hom.:

35444

Cov.:

AF XY:

0.661

AC XY:

49171

AN XY:

74406

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1645

3290

4934

6579

8224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.0

(source)

DANN

Benign

0.60

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over