7-150858914-T-C

Variant names:

• chr7-150858914-T-C
• rs1049748
• NM_001091.4:c.1722T>C

Variant summary

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

The NM_001091.4(AOC1):​c.1722T>C​(p.Pro574Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,611,814 control chromosomes in the GnomAD database, including 152,560 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 0.47 (16792 hom., cov: 32)
  • Exomes 𝑓: 0.43 (135768 hom.)
• Consequence: AOC1 NM_001091.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531
• Publications: 20 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=-0.55).
• BP7: Synonymous conserved (PhyloP=0.531 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001091.4. 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.1722T>C	p.Pro574Pro	synonymous	Exon 3 of 5	NP_001082.2
	AOC1	NM_001272072.2		c.1722T>C	p.Pro574Pro	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.1722T>C	p.Pro574Pro	synonymous	Exon 3 of 5	ENSP00000354193.4
	AOC1	ENST00000416793.6	TSL:1	c.1722T>C	p.Pro574Pro	synonymous	Exon 3 of 5	ENSP00000411613.2
	AOC1	ENST00000467291.5	TSL:5	c.1722T>C	p.Pro574Pro	synonymous	Exon 5 of 7	ENSP00000418328.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70664 AN: 151764 Hom.: 16755 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.452

GnomAD2 exomes AF: 0.459 AC: 112498 AN: 245058 AF XY: 0.458

Gnomad AFR exome AF: 0.552

Gnomad AMR exome AF: 0.498

Gnomad ASJ exome AF: 0.466

Gnomad EAS exome AF: 0.580

Gnomad FIN exome AF: 0.431

Gnomad NFE exome AF: 0.407

Gnomad OTH exome AF: 0.440

GnomAD4 exome AF: 0.427 AC: 622815 AN: 1459932 Hom.: 135768 Cov.: 75 AF XY: 0.430 AC XY: 311890 AN XY: 726104

African (AFR) AF: 0.546 AC: 18277 AN: 33468

American (AMR) AF: 0.496 AC: 22035 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 12012 AN: 26080

East Asian (EAS) AF: 0.612 AC: 24273 AN: 39656

South Asian (SAS) AF: 0.509 AC: 43798 AN: 86072

European-Finnish (FIN) AF: 0.424 AC: 22586 AN: 53240

Middle Eastern (MID) AF: 0.442 AC: 2545 AN: 5764

European-Non Finnish (NFE) AF: 0.406 AC: 450699 AN: 1110928

Other (OTH) AF: 0.441 AC: 26590 AN: 60340

GnomAD4 genome AF: 0.466 AC: 70764 AN: 151882 Hom.: 16792 Cov.: 32 AF XY: 0.469 AC XY: 34811 AN XY: 74208

African (AFR) AF: 0.545 AC: 22573 AN: 41418

American (AMR) AF: 0.479 AC: 7313 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3466

East Asian (EAS) AF: 0.581 AC: 2987 AN: 5142

South Asian (SAS) AF: 0.511 AC: 2456 AN: 4810

European-Finnish (FIN) AF: 0.437 AC: 4617 AN: 10576

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27833 AN: 67898

Other (OTH) AF: 0.457 AC: 960 AN: 2102

Alfa AF: 0.429 Hom.: 20610

Bravo AF: 0.473

Asia WGS AF: 0.545 AC: 1892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.6
DANN	Benign	0.54
PhyloP100		0.53
Mutation Taster		=78/22	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: rs1049748; hg19: chr7-150556002;