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:

ENSG00000285955 (HGNC:58122):

ENSG00000285955 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMS2	NM_001099667.3 link	c.298-26T>C		intron_variant	Intron 1 of 1	ENST00000528446.1	NP_001093137.1	P0C7Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMS2	ENST00000528446.1 link	c.298-26T>C		intron_variant	Intron 1 of 1	1	NM_001099667.3	ENSP00000436682.1		P0C7Q2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over