dbSNP rs36213074: ARMS2:c.298-26T>C (chr10-122456881-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001099667.3(ARMS2):c.298-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,545,522 control chromosomes in the GnomAD database, including 11,478 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.093 ( 849 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10629 hom. )

Consequence

ARMS2
NM_001099667.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.18

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.298-26T>C		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.298-26T>C	intron	N/A	ENSP00000436682.1	P0C7Q2
HTRA1-AS1	ENST00000647969.1		n.182+1614A>G	intron	N/A
HTRA1-AS1	ENST00000650300.1		n.1852+1614A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0929

AC:

14110

AN:

151952

Hom.:

850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0366

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.0945

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.00655

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.0718

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.110

GnomAD2 exomes

AF:

0.105

AC:

15831

AN:

150120

AF XY:

0.110

show subpopulations

Gnomad AFR exome

AF:

0.0327

Gnomad AMR exome

AF:

0.0683

Gnomad ASJ exome

AF:

0.175

Gnomad EAS exome

AF:

0.00767

Gnomad FIN exome

AF:

0.0813

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.128

GnomAD4 exome

AF:

0.118

AC:

164139

AN:

1393450

Hom.:

10629

Cov.:

AF XY:

0.119

AC XY:

81812

AN XY:

687286

show subpopulations

African (AFR)

AF:

0.0342

AC:

1079

AN:

31524

American (AMR)

AF:

0.0718

AC:

2552

AN:

35528

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

4371

AN:

25116

East Asian (EAS)

AF:

0.00406

AC:

145

AN:

35724

South Asian (SAS)

AF:

0.143

AC:

11206

AN:

78534

European-Finnish (FIN)

AF:

0.0847

AC:

4167

AN:

49210

Middle Eastern (MID)

AF:

0.179

AC:

1014

AN:

5670

European-Non Finnish (NFE)

AF:

0.124

AC:

133039

AN:

1074312

Other (OTH)

AF:

0.114

AC:

6566

AN:

57832

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

6175

12350

18526

24701

30876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4792

9584

14376

19168

23960

<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:

0.0928

AC:

14106

AN:

152072

Hom.:

849

Cov.:

AF XY:

0.0908

AC XY:

6752

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0366

AC:

1514

AN:

41412

American (AMR)

AF:

0.0943

AC:

1441

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

631

AN:

3468

East Asian (EAS)

AF:

0.00676

AC:

AN:

5180

South Asian (SAS)

AF:

0.149

AC:

718

AN:

4820

European-Finnish (FIN)

AF:

0.0718

AC:

760

AN:

10586

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8561

AN:

68012

Other (OTH)

AF:

0.109

AC:

229

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

631

1261

1892

2522

3153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.107

Hom.:

1475

Bravo

AF:

0.0880

Asia WGS

AF:

0.0810

AC:

282

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.1

(source)

DANN

Benign

0.65

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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