rs1049793

Positions:

• chr7-150860577-C-G
• chr7-150860577-C-T

Variant summary

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

The NM_001091.4(AOC1):​c.1933C>G​(p.His645Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,613,582 control chromosomes in the GnomAD database, including 93,694 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (11216 hom., cov: 31)
  • Exomes 𝑓: 0.33 (82478 hom.)
• Consequence: AOC1 NM_001091.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.887249E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOC1	NM_001091.4	c.1933C>G	p.His645Asp	missense_variant	4/5	ENST00000360937.9	NP_001082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AOC1	ENST00000360937.9	c.1933C>G	p.His645Asp	missense_variant	4/5	1	NM_001091.4	ENSP00000354193.4

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56512 AN: 151786 Hom.: 11208 Cov.: 31

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.351

GnomAD3 exomes AF: 0.370 AC: 92361 AN: 249490 Hom.: 18341 AF XY: 0.369 AC XY: 49949 AN XY: 135378

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.421

Gnomad ASJ exome AF: 0.391

Gnomad EAS exome AF: 0.502

Gnomad SAS exome AF: 0.491

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.326 AC: 476088 AN: 1461678 Hom.: 82478 Cov.: 55 AF XY: 0.330 AC XY: 239760 AN XY: 727158

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.372 AC: 56548 AN: 151904 Hom.: 11216 Cov.: 31 AF XY: 0.374 AC XY: 27761 AN XY: 74248

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.351

Alfa AF: 0.320 Hom.: 6156

Bravo AF: 0.381

TwinsUK AF: 0.299 AC: 1108

ALSPAC AF: 0.303 AC: 1166

ESP6500AA AF: 0.465 AC: 1945

ESP6500EA AF: 0.300 AC: 2531

ExAC AF: 0.370 AC: 44734

Asia WGS AF: 0.470 AC: 1632 AN: 3478

EpiCase AF: 0.294

EpiControl AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.4
DANN	Benign	0.86
DEOGEN2	Benign	0.053	T;T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.022	.;T;.;T
MetaRNN	Benign	0.00029	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.8	N;N;N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	3.0	N;N;N;N
REVEL	Benign	0.28
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.042
MPC		0.29
ClinPred		0.0047	T
GERP RS		3.1
Varity_R		0.086
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs1049793; hg19: chr7-150557665; COSMIC: COSV62867576; COSMIC: COSV62867576;