rs10490923
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001099667.3(ARMS2):c.8G>A(p.Arg3His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,550 control chromosomes in the GnomAD database, including 11,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.093 ( 856 hom., cov: 31)
Exomes 𝑓: 0.12 ( 11079 hom. )
Consequence
ARMS2
NM_001099667.3 missense
NM_001099667.3 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: -0.560
Genes affected
ARMS2 (HGNC:32685): (age-related maculopathy susceptibility 2) This gene encodes a small secreted protein specific to primates. This protein is a component of the choroidal extracellular matrix of the eye. Mutations in this gene are associated with age-related macular degeneration. [provided by RefSeq, Sep 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0013993382).
BP6
?
Variant 10-122454735-G-A is Benign according to our data. Variant chr10-122454735-G-A is described in ClinVar as [Benign]. Clinvar id is 299028.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARMS2 | NM_001099667.3 | c.8G>A | p.Arg3His | missense_variant | 1/2 | ENST00000528446.1 | |
LOC105378525 | XR_946382.3 | n.1874+3760C>T | intron_variant, non_coding_transcript_variant | ||||
LOC105378525 | XR_946383.3 | n.1852+3760C>T | intron_variant, non_coding_transcript_variant | ||||
LOC105378525 | XR_946384.3 | n.1601+3760C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARMS2 | ENST00000528446.1 | c.8G>A | p.Arg3His | missense_variant | 1/2 | 1 | NM_001099667.3 | P1 | |
ENST00000650300.1 | n.1852+3760C>T | intron_variant, non_coding_transcript_variant | |||||||
ENST00000647969.1 | n.182+3760C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0931 AC: 14152AN: 152014Hom.: 857 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
14152
AN:
152014
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.105 AC: 26213AN: 249074Hom.: 1703 AF XY: 0.110 AC XY: 14923AN XY: 135126
GnomAD3 exomes
AF:
AC:
26213
AN:
249074
Hom.:
AF XY:
AC XY:
14923
AN XY:
135126
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.119 AC: 173203AN: 1461418Hom.: 11079 Cov.: 32 AF XY: 0.120 AC XY: 87176AN XY: 727008
GnomAD4 exome
AF:
AC:
173203
AN:
1461418
Hom.:
Cov.:
32
AF XY:
AC XY:
87176
AN XY:
727008
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0930 AC: 14147AN: 152132Hom.: 856 Cov.: 31 AF XY: 0.0913 AC XY: 6788AN XY: 74368
GnomAD4 genome
?
AF:
AC:
14147
AN:
152132
Hom.:
Cov.:
31
AF XY:
AC XY:
6788
AN XY:
74368
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
481
ALSPAC
AF:
AC:
455
ESP6500AA
AF:
AC:
148
ESP6500EA
AF:
AC:
1091
ExAC
?
AF:
AC:
12880
Asia WGS
AF:
AC:
284
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Age related macular degeneration 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
P
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at