rs35070995

Variant names:

• chr7-150860619-A-C
• rs35070995
• NM_001091.4:c.1975A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.77
• Publications: 8 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 -20 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 VariationId is 792093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 gene

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.1975A>C	p.Asn659His	missense	Exon 4 of 5	NP_001082.2	P19801-1
	AOC1	NM_001272072.2		c.2032A>C	p.Asn678His	missense	Exon 4 of 5	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.1975A>C	p.Asn659His	missense	Exon 4 of 5	ENSP00000354193.4	P19801-1
	AOC1	ENST00000416793.6	TSL:1	c.2032A>C	p.Asn678His	missense	Exon 4 of 5	ENSP00000411613.2	P19801-2
	AOC1	ENST00000941409.1		c.2032A>C	p.Asn678His	missense	Exon 5 of 6	ENSP00000611468.1

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

GnomAD2 exomes AF: 0.00158 AC: 394 AN: 249488 AF XY: 0.00124

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 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

African (AFR) AF: 0.0237 AC: 794 AN: 33476

American (AMR) AF: 0.00112 AC: 50 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111906

Other (OTH) AF: 0.00108 AC: 65 AN: 60394

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

African (AFR) AF: 0.0225 AC: 933 AN: 41504

American (AMR) AF: 0.00164 AC: 25 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67968

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00222 Hom.: 10

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.17
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0085	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		2.8
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.092
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	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
Mutation Taster		=93/7	polymorphism

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: rs35070995; hg19: chr7-150557707;