Genetic Variant NM_001091.4:c.47C>T (chr7-150856517-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_001091.4(AOC1):c.47C>T(p.Thr16Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,618 control chromosomes in the GnomAD database, including 62,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 9422 hom., cov: 32)

Exomes 𝑓: 0.26 ( 53086 hom. )

Consequence

AOC1
NM_001091.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.132

Publications

66 publications found

Variant links:

Genes affected

AOC1 (HGNC:80): (amine oxidase copper containing 1) This gene encodes a metal-binding membrane glycoprotein that oxidatively deaminates putrescine, histamine, and related compounds. The encoded protein is inhibited by amiloride, a diuretic that acts by closing epithelial sodium ion channels. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]

AOC1 links:

ENSG00000289052 (HGNC:):

ENSG00000289052 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 (MetaRNN=3.31944E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOC1	NM_001091.4 link	c.47C>T	p.Thr16Met	missense_variant	Exon 2 of 5	ENST00000360937.9	NP_001082.2	P19801-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOC1	ENST00000360937.9 link	c.47C>T	p.Thr16Met	missense_variant	Exon 2 of 5	1	NM_001091.4	ENSP00000354193.4		P19801-1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49511

AN:

151884

Hom.:

9397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.519

Gnomad AMI

AF:

0.371

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.287

GnomAD2 exomes

AF:

0.261

AC:

64895

AN:

248794

AF XY:

0.260

show subpopulations

Gnomad AFR exome

AF:

0.532

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.287

Gnomad NFE exome

AF:

0.264

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.262

AC:

382663

AN:

1461616

Hom.:

53086

Cov.:

AF XY:

0.261

AC XY:

189675

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.524

AC:

17544

AN:

33476

American (AMR)

AF:

0.180

AC:

8034

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

7334

AN:

26124

East Asian (EAS)

AF:

0.114

AC:

4536

AN:

39700

South Asian (SAS)

AF:

0.262

AC:

22589

AN:

86250

European-Finnish (FIN)

AF:

0.289

AC:

15414

AN:

53346

Middle Eastern (MID)

AF:

0.231

AC:

1330

AN:

5768

European-Non Finnish (NFE)

AF:

0.261

AC:

290055

AN:

1111852

Other (OTH)

AF:

0.262

AC:

15827

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

16813

33626

50438

67251

84064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9808

19616

29424

39232

49040

<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:

0.326

AC:

49577

AN:

152002

Hom.:

9422

Cov.:

AF XY:

0.323

AC XY:

24038

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.520

AC:

21537

AN:

41452

American (AMR)

AF:

0.229

AC:

3495

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

994

AN:

3464

East Asian (EAS)

AF:

0.123

AC:

635

AN:

5160

South Asian (SAS)

AF:

0.262

AC:

1260

AN:

4816

European-Finnish (FIN)

AF:

0.282

AC:

2984

AN:

10588

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.260

AC:

17660

AN:

67932

Other (OTH)

AF:

0.283

AC:

597

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1575

3151

4726

6302

7877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.270

Hom.:

17788

Bravo

AF:

0.331

TwinsUK

AF:

0.257

AC:

953

ALSPAC

AF:

0.250

AC:

962

ESP6500AA

AF:

0.508

AC:

1966

ESP6500EA

AF:

0.267

AC:

2203

ExAC

AF:

0.270

AC:

32562

Asia WGS

AF:

0.215

AC:

752

AN:

3478

EpiCase

AF:

0.265

EpiControl

AF:

0.255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.5

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.086

T;T;.;T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.23

.;T;T;.;T;T

MetaRNN

Benign

0.000033

T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.84

N;N;.;N;N;.

PhyloP100

-0.13

PrimateAI

Benign

0.31

PROVEAN

Benign

0.36

N;N;N;N;N;N

REVEL

Benign

0.024

Sift

Benign

0.21

T;T;T;T;T;T

Sift4G

Benign

0.18

T;T;T;T;T;T

Polyphen

0.0010

B;B;.;B;.;.

Vest4

0.030

MPC

0.22

ClinPred

0.0019

GERP RS

-0.64

Varity_R

0.013

gMVP

0.22

Mutation Taster

=97/3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over