rs7088128

Variant names:

• chr10-122456894-A-G
• rs7088128
• NM_001099667.3:c.298-13A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-122456894-A-G
• chr10-122456894-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001099667.3(ARMS2):​c.298-13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,507,780 control chromosomes in the GnomAD database, including 10,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (922 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9856 hom.)
• Consequence: ARMS2 NM_001099667.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.213
• Publications: 4 publications found

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]

ENSG00000285955 (HGNC:58122):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-122456894-A-G is Benign according to our data. Variant chr10-122456894-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 299031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ARMS2	NM_001099667.3	c.298-13A>G		intron_variant	Intron 1 of 1	ENST00000528446.1	NP_001093137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMS2	ENST00000528446.1	c.298-13A>G		intron_variant	Intron 1 of 1	1	NM_001099667.3	ENSP00000436682.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15534 AN: 151044 Hom.: 924 Cov.: 32

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.0997

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.00658

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.119

GnomAD2 exomes AF: 0.116 AC: 16199 AN: 139318 AF XY: 0.121

Gnomad AFR exome AF: 0.0739

Gnomad AMR exome AF: 0.0803

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.00831

Gnomad FIN exome AF: 0.0838

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.122 AC: 164861 AN: 1356616 Hom.: 9856 Cov.: 33 AF XY: 0.123 AC XY: 82084 AN XY: 669312

African (AFR) AF: 0.0692 AC: 2097 AN: 30318

American (AMR) AF: 0.0780 AC: 2619 AN: 33592

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 4336 AN: 24348

East Asian (EAS) AF: 0.00429 AC: 145 AN: 33764

South Asian (SAS) AF: 0.147 AC: 11163 AN: 76150

European-Finnish (FIN) AF: 0.0870 AC: 4172 AN: 47930

Middle Eastern (MID) AF: 0.182 AC: 1015 AN: 5582

European-Non Finnish (NFE) AF: 0.126 AC: 132624 AN: 1048846

Other (OTH) AF: 0.119 AC: 6690 AN: 56086

GnomAD4 genome AF: 0.103 AC: 15532 AN: 151164 Hom.: 922 Cov.: 32 AF XY: 0.100 AC XY: 7381 AN XY: 73770

African (AFR) AF: 0.0696 AC: 2863 AN: 41150

American (AMR) AF: 0.0995 AC: 1506 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3468

East Asian (EAS) AF: 0.00679 AC: 35 AN: 5152

South Asian (SAS) AF: 0.149 AC: 712 AN: 4776

European-Finnish (FIN) AF: 0.0730 AC: 761 AN: 10428

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.126 AC: 8561 AN: 67774

Other (OTH) AF: 0.118 AC: 246 AN: 2084

Alfa AF: 0.0982 Hom.: 334

Bravo AF: 0.113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Age related macular degeneration 8 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Macular degeneration Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.85
DANN	Benign	0.63
PhyloP100		-0.21
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: rs7088128; hg19: chr10-124216410;