chr10-122457306-T-G

Variant names:

• chr10-122457306-T-G
• rs4752698
• NM_001099667.3:c.*373T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0280
• Publications: 2 publications found

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]

ENSG00000285955 (HGNC:58122):

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMS2	NM_001099667.3	c.*373T>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000528446.1	NP_001093137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMS2	ENST00000528446.1	c.*373T>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001099667.3	ENSP00000436682.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 14210 AN: 141340 Hom.: 1217 Cov.: 31

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.: 0 AF XY: 0.127 AC XY: 3934 AN XY: 30906

African (AFR) AF: 0.0364 AC: 76 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: 9 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: 62 AN: 318

European-Non Finnish (NFE) AF: 0.135 AC: 5650 AN: 41910

Other (OTH) AF: 0.128 AC: 555 AN: 4334

GnomAD4 genome AF: 0.100 AC: 14205 AN: 141442 Hom.: 1215 Cov.: 31 AF XY: 0.0981 AC XY: 6773 AN XY: 69026

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: 36 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: 61 AN: 276

European-Non Finnish (NFE) AF: 0.135 AC: 8660 AN: 64276

Other (OTH) AF: 0.121 AC: 240 AN: 1976

Alfa AF: 0.126 Hom.: 346

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Age related macular degeneration 8 Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Macular degeneration Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.49
PhyloP100		0.028
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4752698; hg19: chr10-124216822;