7-150858827-A-G

Variant names:

• chr7-150858827-A-G
• rs10893
• NM_001091.4:c.1635A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001272072.2(AOC1):​c.1635A>G​(p.Pro545Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,612,818 control chromosomes in the GnomAD database, including 97,321 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 0.38 (11842 hom., cov: 32)
  • Exomes 𝑓: 0.33 (85479 hom.)
• Consequence: AOC1 NM_001272072.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.31
• Publications: 31 publications found

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]

ENSG00000289052 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-4.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001272072.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOC1	NM_001091.4	MANE Select	c.1635A>G	p.Pro545Pro	synonymous	Exon 3 of 5	NP_001082.2
	AOC1	NM_001272072.2		c.1635A>G	p.Pro545Pro	synonymous	Exon 3 of 5	NP_001259001.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOC1	ENST00000360937.9	TSL:1 MANE Select	c.1635A>G	p.Pro545Pro	synonymous	Exon 3 of 5	ENSP00000354193.4
	AOC1	ENST00000416793.6	TSL:1	c.1635A>G	p.Pro545Pro	synonymous	Exon 3 of 5	ENSP00000411613.2
	AOC1	ENST00000941409.1		c.1635A>G	p.Pro545Pro	synonymous	Exon 4 of 6	ENSP00000611468.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58058 AN: 151852 Hom.: 11832 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.358

GnomAD2 exomes AF: 0.375 AC: 93370 AN: 248826 AF XY: 0.374

Gnomad AFR exome AF: 0.498

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.504

Gnomad FIN exome AF: 0.325

Gnomad NFE exome AF: 0.301

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.332 AC: 485414 AN: 1460848 Hom.: 85479 Cov.: 53 AF XY: 0.336 AC XY: 244130 AN XY: 726596

African (AFR) AF: 0.501 AC: 16783 AN: 33472

American (AMR) AF: 0.423 AC: 18887 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 10298 AN: 26100

East Asian (EAS) AF: 0.538 AC: 21324 AN: 39658

South Asian (SAS) AF: 0.490 AC: 42238 AN: 86210

European-Finnish (FIN) AF: 0.323 AC: 17239 AN: 53382

Middle Eastern (MID) AF: 0.296 AC: 1706 AN: 5764

European-Non Finnish (NFE) AF: 0.302 AC: 335871 AN: 1111240

Other (OTH) AF: 0.349 AC: 21068 AN: 60358

GnomAD4 genome AF: 0.382 AC: 58102 AN: 151970 Hom.: 11842 Cov.: 32 AF XY: 0.384 AC XY: 28511 AN XY: 74296

African (AFR) AF: 0.500 AC: 20730 AN: 41448

American (AMR) AF: 0.386 AC: 5894 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1413 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2611 AN: 5156

South Asian (SAS) AF: 0.493 AC: 2372 AN: 4814

European-Finnish (FIN) AF: 0.320 AC: 3390 AN: 10586

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20467 AN: 67906

Other (OTH) AF: 0.358 AC: 755 AN: 2108

Alfa AF: 0.331 Hom.: 29287

Bravo AF: 0.392

Asia WGS AF: 0.470 AC: 1631 AN: 3478

EpiCase AF: 0.300

EpiControl AF: 0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.38
PhyloP100		-4.3
Mutation Taster		=99/1	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: rs10893; hg19: chr7-150555915; COSMIC: COSV62869446; COSMIC: COSV62869446;