rs1049742

Variant names:

• chr7-150857465-C-T
• rs1049742
• NM_001091.4:c.995C>T

Variant summary

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

The NM_001091.4(AOC1):​c.995C>T​(p.Ser332Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 1,612,628 control chromosomes in the GnomAD database, including 4,776 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.073 (433 hom., cov: 33)
  • Exomes 𝑓: 0.071 (4343 hom.)
• Consequence: AOC1 NM_001091.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039739013).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOC1	NM_001091.4	c.995C>T	p.Ser332Phe	missense_variant	Exon 2 of 5	ENST00000360937.9	NP_001082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOC1	ENST00000360937.9	c.995C>T	p.Ser332Phe	missense_variant	Exon 2 of 5	1	NM_001091.4	ENSP00000354193.4

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11063 AN: 152194 Hom.: 433 Cov.: 33

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0462

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0279

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0670

GnomAD3 exomes AF: 0.0575 AC: 14200 AN: 247160 Hom.: 547 AF XY: 0.0567 AC XY: 7623 AN XY: 134528

Gnomad AFR exome AF: 0.0920

Gnomad AMR exome AF: 0.0301

Gnomad ASJ exome AF: 0.0482

Gnomad EAS exome AF: 0.00179

Gnomad SAS exome AF: 0.0312

Gnomad FIN exome AF: 0.0711

Gnomad NFE exome AF: 0.0757

Gnomad OTH exome AF: 0.0526

GnomAD4 exome AF: 0.0706 AC: 103135 AN: 1460316 Hom.: 4343 Cov.: 34 AF XY: 0.0688 AC XY: 49983 AN XY: 726454

Gnomad4 AFR exome AF: 0.0920

Gnomad4 AMR exome AF: 0.0324

Gnomad4 ASJ exome AF: 0.0511

Gnomad4 EAS exome AF: 0.000806

Gnomad4 SAS exome AF: 0.0299

Gnomad4 FIN exome AF: 0.0729

Gnomad4 NFE exome AF: 0.0782

Gnomad4 OTH exome AF: 0.0621

GnomAD4 genome AF: 0.0726 AC: 11062 AN: 152312 Hom.: 433 Cov.: 33 AF XY: 0.0697 AC XY: 5188 AN XY: 74484

Gnomad4 AFR AF: 0.0927

Gnomad4 AMR AF: 0.0461

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0282

Gnomad4 FIN AF: 0.0650

Gnomad4 NFE AF: 0.0766

Gnomad4 OTH AF: 0.0663

Alfa AF: 0.0702 Hom.: 962

Bravo AF: 0.0724

TwinsUK AF: 0.0823 AC: 305

ALSPAC AF: 0.0732 AC: 282

ESP6500AA AF: 0.0861 AC: 379

ESP6500EA AF: 0.0738 AC: 634

ExAC AF: 0.0591 AC: 7172

Asia WGS AF: 0.0210 AC: 76 AN: 3478

EpiCase AF: 0.0705

EpiControl AF: 0.0706

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;T;.;T
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.33	N
LIST_S2	Uncertain	0.89	.;D;.;D;T
MetaRNN	Benign	0.0040	T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.0	M;M;M;M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D;D;D;T;D
Sift4G	Uncertain	0.030	D;D;D;D;D
Polyphen		0.99	D;D;D;.;.
Vest4		0.089
MPC		0.83
ClinPred		0.037	T
GERP RS		5.0
Varity_R		0.51
gMVP		0.70

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: rs1049742; hg19: chr7-150554553;