rs36212732

Variant names:

• chr10-122455682-A-G
• rs36212732
• NM_001099667.3:c.297+658A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099667.3(ARMS2):​c.297+658A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,090 control chromosomes in the GnomAD database, including 4,417 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 0.24 (4417 hom., cov: 32)
• Consequence: ARMS2 NM_001099667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMS2	NM_001099667.3	c.297+658A>G		intron_variant	Intron 1 of 1	ENST00000528446.1	NP_001093137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMS2	ENST00000528446.1	c.297+658A>G		intron_variant	Intron 1 of 1	1	NM_001099667.3	ENSP00000436682.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35740 AN: 151972 Hom.: 4410 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.236

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.235 AC: 35780 AN: 152090 Hom.: 4417 Cov.: 32 AF XY: 0.238 AC XY: 17680 AN XY: 74334

African (AFR) AF: 0.232 AC: 9604 AN: 41474

American (AMR) AF: 0.233 AC: 3559 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 706 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2145 AN: 5156

South Asian (SAS) AF: 0.320 AC: 1538 AN: 4812

European-Finnish (FIN) AF: 0.235 AC: 2487 AN: 10576

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.220 AC: 14926 AN: 67998

Other (OTH) AF: 0.233 AC: 493 AN: 2114

Alfa AF: 0.296 Hom.: 5096

Bravo AF: 0.237

Asia WGS AF: 0.369 AC: 1278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.55
PhyloP100		-0.036
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: rs36212732; hg19: chr10-124215198;