rs12179

Positions:

• chr7-150860534-G-A
• chr7-150860534-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000360937.9(AOC1):​c.1890G>A​(p.Ser630=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,613,522 control chromosomes in the GnomAD database, including 93,764 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 0.37 (11231 hom., cov: 31)
  • Exomes 𝑓: 0.33 (82533 hom.)
• Consequence: AOC1 ENST00000360937.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.58

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]

LOC105375567 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-7.58 with no splicing effect.
• 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.1890G>A	p.Ser630=	synonymous_variant	4/5	ENST00000360937.9	NP_001082.2
LOC105375567	XR_928171.3	n.122+16475C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AOC1	ENST00000360937.9	c.1890G>A	p.Ser630=	synonymous_variant	4/5	1	NM_001091.4	ENSP00000354193	P2

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56553 AN: 151742 Hom.: 11223 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.351

GnomAD3 exomes AF: 0.370 AC: 92370 AN: 249364 Hom.: 18332 AF XY: 0.369 AC XY: 49955 AN XY: 135312

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: 0.321

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.326 AC: 476282 AN: 1461662 Hom.: 82533 Cov.: 53 AF XY: 0.330 AC XY: 239866 AN XY: 727136

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.536

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.373 AC: 56589 AN: 151860 Hom.: 11231 Cov.: 31 AF XY: 0.374 AC XY: 27779 AN XY: 74206

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: 0.317

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.351

Alfa AF: 0.309 Hom.: 11504

Bravo AF: 0.381

Asia WGS AF: 0.470 AC: 1632 AN: 3478

EpiCase AF: 0.295

EpiControl AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.049
DANN	Benign	0.73

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: rs12179; hg19: chr7-150557622; COSMIC: COSV62867568; COSMIC: COSV62867568;