rs35070995

chr7-150860619-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001091.4(AOC1):c.1975A>C(p.Asn659His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,613,882 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0064 (11 hom., cov: 31)
  • Exomes 𝑓: 0.00064 (13 hom.)
• Consequence: AOC1 NM_001091.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.77

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00846684).
• BP6: Variant 7-150860619-A-C is Benign according to our data. Variant chr7-150860619-A-C is described in ClinVar as [Benign]. Clinvar id is 792093.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00637 (969/152118) while in subpopulation AFR AF= 0.0225 (933/41504). AF 95% confidence interval is 0.0213. There are 11 homozygotes in gnomad4. There are 454 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOC1	NM_001091.4	c.1975A>C	p.Asn659His	missense_variant	4/5	ENST00000360937.9
LOC105375567	XR_928171.3	n.122+16390T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOC1	ENST00000360937.9	c.1975A>C	p.Asn659His	missense_variant	4/5	1	NM_001091.4	P2

Frequencies

GnomAD3 genomes AF: 0.00634 AC: 963 AN: 152000 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.00158 AC: 394 AN: 249488 Hom.: 5 AF XY: 0.00124 AC XY: 168 AN XY: 135360

Gnomad AFR exome AF: 0.0223

Gnomad AMR exome AF: 0.000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000826

GnomAD4 exome AF: 0.000642 AC: 939 AN: 1461764 Hom.: 13 Cov.: 39 AF XY: 0.000562 AC XY: 409 AN XY: 727192

Gnomad4 AFR exome AF: 0.0237

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000234

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.00637 AC: 969 AN: 152118 Hom.: 11 Cov.: 31 AF XY: 0.00610 AC XY: 454 AN XY: 74370

Gnomad4 AFR AF: 0.0225

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000950

Alfa AF: 0.00143 Hom.: 1

Bravo AF: 0.00722

ESP6500AA AF: 0.0185 AC: 77

ESP6500EA AF: 0.000355 AC: 3

ExAC AF: 0.00195 AC: 236

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T;T;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.91	D
MetaRNN	Benign	0.0085	T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.3	M;M;M;.
MutationTaster	Benign	0.91	D;D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Benign	0.092
Sift	Uncertain	0.0060	D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.28
MVP		0.29
MPC		0.72
ClinPred		0.066	T
GERP RS		3.9
Varity_R		0.54
gMVP		0.75

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: rs35070995; hg19: chr7-150557707;