Variant chr10-122456978-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001099667.3(ARMS2):c.*45T>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 0.000781 in 1,551,140 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 8 hom. )

Consequence

ARMS2
NM_001099667.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.37

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:):

ENSG00000285955 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 10-122456978-T-G is Benign according to our data. Variant chr10-122456978-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 879637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMS2	NM_001099667.3 linkuse as main transcript	c.*45T>G		3_prime_UTR_variant	2/2	ENST00000528446.1	NP_001093137.1	P0C7Q2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARMS2	ENST00000528446.1 linkuse as main transcript	c.*45T>G	3_prime_UTR_variant	2/2	1	NM_001099667.3	ENSP00000436682.1	P0C7Q2
ENSG00000285955	ENST00000647969.1 linkuse as main transcript	n.182+1517A>C	intron_variant
ENSG00000285955	ENST00000650300.1 linkuse as main transcript	n.1852+1517A>C	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00388

AC:

590

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000976

AC:

148

AN:

151642

Hom.:

AF XY:

0.000870

AC XY:

AN XY:

80432

show subpopulations

Gnomad AFR exome

AF:

0.0136

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000177

Gnomad FIN exome

AF:

0.0000655

Gnomad NFE exome

AF:

0.000122

Gnomad OTH exome

AF:

0.000466

GnomAD4 exome

AF:

0.000437

AC:

611

AN:

1398862

Hom.:

Cov.:

AF XY:

0.000422

AC XY:

291

AN XY:

689896

show subpopulations

Gnomad4 AFR exome

AF:

0.0136

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000759

Gnomad4 FIN exome

AF:

0.0000609

Gnomad4 NFE exome

AF:

0.0000501

Gnomad4 OTH exome

AF:

0.00112

GnomAD4 genome

AF:

0.00395

AC:

601

AN:

152278

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

280

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0134

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00435

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Age related macular degeneration 8

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.55

DANN

Benign

0.73

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