dbSNP rs4752698: ARMS2:c.*373T>G (chr10-122457306-T-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.*373T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 203,018 control chromosomes in the GnomAD database, including 1,805 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 ( 1215 hom., cov: 31)

Exomes 𝑓: 0.12 ( 590 hom. )

Consequence

ARMS2
NM_001099667.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0280

Publications

2 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 10-122457306-T-G is Benign according to our data. Variant chr10-122457306-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 299038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 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.*373T>G		3_prime_UTR	Exon 2 of 2	NP_001093137.1	P0C7Q2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARMS2	ENST00000528446.1	TSL:1 MANE Select	c.*373T>G	3_prime_UTR	Exon 2 of 2	ENSP00000436682.1	P0C7Q2
HTRA1-AS1	ENST00000647969.1		n.182+1189A>C	intron	N/A
HTRA1-AS1	ENST00000650300.1		n.1852+1189A>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

14210

AN:

141340

Hom.:

1217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0393

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.00841

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.0763

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.123

GnomAD4 exome

AF:

0.124

AC:

7648

AN:

61576

Hom.:

590

Cov.:

AF XY:

0.127

AC XY:

3934

AN XY:

30906

show subpopulations

African (AFR)

AF:

0.0364

AC:

AN:

2086

American (AMR)

AF:

0.0856

AC:

180

AN:

2102

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

454

AN:

2592

East Asian (EAS)

AF:

0.00293

AC:

AN:

3076

South Asian (SAS)

AF:

0.194

AC:

362

AN:

1866

European-Finnish (FIN)

AF:

0.0911

AC:

300

AN:

3292

Middle Eastern (MID)

AF:

0.195

AC:

AN:

318

European-Non Finnish (NFE)

AF:

0.135

AC:

5650

AN:

41910

Other (OTH)

AF:

0.128

AC:

555

AN:

4334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

322

644

966

1288

1610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.100

AC:

14205

AN:

141442

Hom.:

1215

Cov.:

AF XY:

0.0981

AC XY:

6773

AN XY:

69026

show subpopulations

African (AFR)

AF:

0.0393

AC:

1513

AN:

38480

American (AMR)

AF:

0.101

AC:

1435

AN:

14152

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

639

AN:

3334

East Asian (EAS)

AF:

0.00867

AC:

AN:

4152

South Asian (SAS)

AF:

0.171

AC:

706

AN:

4132

European-Finnish (FIN)

AF:

0.0763

AC:

750

AN:

9828

Middle Eastern (MID)

AF:

0.221

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.135

AC:

8660

AN:

64276

Other (OTH)

AF:

0.121

AC:

240

AN:

1976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.553

Heterozygous variant carriers

522

1044

1565

2087

2609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.126

Hom.:

346

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

3.2

(source)

DANN

Benign

0.49

PhyloP100

0.028

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

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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