rs36213074

Positions:

• chr10-122456881-T-C
• chr10-122456881-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099667.3(ARMS2):​c.298-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,545,522 control chromosomes in the GnomAD database, including 11,478 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 0.093 (849 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10629 hom.)
• Consequence: ARMS2 NM_001099667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMS2	NM_001099667.3	c.298-26T>C		intron_variant		ENST00000528446.1	NP_001093137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMS2	ENST00000528446.1	c.298-26T>C		intron_variant		1	NM_001099667.3	ENSP00000436682.1
ENSG00000285955	ENST00000647969.1	n.182+1614A>G		intron_variant
ENSG00000285955	ENST00000650300.1	n.1852+1614A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14110 AN: 151952 Hom.: 850 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.0945

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.110

GnomAD3 exomes AF: 0.105 AC: 15831 AN: 150120 Hom.: 1047 AF XY: 0.110 AC XY: 8740 AN XY: 79484

Gnomad AFR exome AF: 0.0327

Gnomad AMR exome AF: 0.0683

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.00767

Gnomad SAS exome AF: 0.143

Gnomad FIN exome AF: 0.0813

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.118 AC: 164139 AN: 1393450 Hom.: 10629 Cov.: 33 AF XY: 0.119 AC XY: 81812 AN XY: 687286

Gnomad4 AFR exome AF: 0.0342

Gnomad4 AMR exome AF: 0.0718

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.00406

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.0847

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.0928 AC: 14106 AN: 152072 Hom.: 849 Cov.: 32 AF XY: 0.0908 AC XY: 6752 AN XY: 74364

Gnomad4 AFR AF: 0.0366

Gnomad4 AMR AF: 0.0943

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.00676

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0718

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0880 Hom.: 208

Bravo AF: 0.0880

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs36213074; hg19: chr10-124216397;