rs2268999

Variant names:

• chr7-150855877-A-T
• rs2268999
• NM_001091.4:c.-16-578A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001091.4(AOC1):​c.-16-578A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,434 control chromosomes in the GnomAD database, including 9,704 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 0.33 (9704 hom., cov: 32)
• Consequence: AOC1 NM_001091.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOC1	NM_001091.4	MANE Select	c.-16-578A>T		intron	N/A	NP_001082.2	P19801-1
	AOC1	NM_001272072.2		c.-16-578A>T		intron	N/A	NP_001259001.1	P19801-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOC1	ENST00000360937.9	TSL:1 MANE Select	c.-16-578A>T		intron	N/A	ENSP00000354193.4	P19801-1
	AOC1	ENST00000416793.6	TSL:1	c.-16-578A>T		intron	N/A	ENSP00000411613.2	P19801-2
	AOC1	ENST00000941409.1		c.-16-578A>T		intron	N/A	ENSP00000611468.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 49963 AN: 151314 Hom.: 9673 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.330 AC: 50037 AN: 151434 Hom.: 9704 Cov.: 32 AF XY: 0.327 AC XY: 24217 AN XY: 74034

African (AFR) AF: 0.534 AC: 22126 AN: 41396

American (AMR) AF: 0.229 AC: 3484 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 968 AN: 3458

East Asian (EAS) AF: 0.121 AC: 626 AN: 5166

South Asian (SAS) AF: 0.237 AC: 1140 AN: 4800

European-Finnish (FIN) AF: 0.287 AC: 3028 AN: 10540

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17656 AN: 67554

Other (OTH) AF: 0.284 AC: 595 AN: 2096

Alfa AF: 0.302 Hom.: 981

Bravo AF: 0.335

Asia WGS AF: 0.201 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.098
DANN	Benign	0.44
PhyloP100		-2.5
Mutation Taster		=100/0	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: rs2268999; hg19: chr7-150552965;