dbSNP rs7088128: ARMS2:c.298-13A>G (chr10-122456894-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.213

Publications

4 publications found

Variant links:

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]

ARMS2 links:

HTRA1-AS1 (HGNC:58122):

HTRA1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099667.3. 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
	ARMS2	NM_001099667.3	MANE Select	c.298-13A>G		intron	N/A	NP_001093137.1	P0C7Q2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARMS2	ENST00000528446.1	TSL:1 MANE Select	c.298-13A>G	intron	N/A	ENSP00000436682.1	P0C7Q2
HTRA1-AS1	ENST00000647969.1		n.182+1601T>C	intron	N/A
HTRA1-AS1	ENST00000650300.1		n.1852+1601T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15534

AN:

151044

Hom.:

924

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.123

AC XY:

82084

AN XY:

669312

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

6553

13106

19658

26211

32764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4838

9676

14514

19352

24190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.103

AC:

15532

AN:

151164

Hom.:

922

Cov.:

AF XY:

0.100

AC XY:

7381

AN XY:

73770

show subpopulations

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:

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.126

AC:

8561

AN:

67774

Other (OTH)

AF:

0.118

AC:

246

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

699

1398

2097

2796

3495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0982

Hom.:

334

Bravo

AF:

0.113

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Age related macular degeneration 8 (1)

Macular degeneration (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.85

(source)

DANN

Benign

0.63

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over