Variant 10-122457306-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMS2	NM_001099667.3 linkuse as main transcript	c.*373T>G		3_prime_UTR_variant	2/2	ENST00000528446.1	NP_001093137.1
LOC105378525	XR_946382.3 linkuse as main transcript	n.1874+1189A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
ARMS2	ENST00000528446.1 linkuse as main transcript	c.*373T>G	3_prime_UTR_variant	2/2	1	NM_001099667.3	ENSP00000436682	P1
	ENST00000650300.1 linkuse as main transcript	n.1852+1189A>C	intron_variant, non_coding_transcript_variant
	ENST00000647969.1 linkuse as main transcript	n.182+1189A>C	intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome

AF:

0.0364

Gnomad4 AMR exome

AF:

0.0856

Gnomad4 ASJ exome

AF:

0.175

Gnomad4 EAS exome

AF:

0.00293

Gnomad4 SAS exome

AF:

0.194

Gnomad4 FIN exome

AF:

0.0911

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.100

AC:

14205

AN:

141442

Hom.:

1215

Cov.:

AF XY:

0.0981

AC XY:

6773

AN XY:

69026

show subpopulations

Gnomad4 AFR

AF:

0.0393

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.00867

Gnomad4 SAS

AF:

0.171

Gnomad4 FIN

AF:

0.0763

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.126

Hom.:

346

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Age related macular degeneration 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

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

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Macular degeneration

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.2

DANN

Benign

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over