rs36213074

Variant names:

• chr10-122456881-T-C
• rs36213074
• NM_001099667.3:c.298-26T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-122456881-T-C
• chr10-122456881-T-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.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
• Publications: 6 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]

HTRA1-AS1 (HGNC:58122):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099667.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMS2	NM_001099667.3	MANE Select	c.298-26T>C		intron	N/A	NP_001093137.1	P0C7Q2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMS2	ENST00000528446.1	TSL:1 MANE Select	c.298-26T>C		intron	N/A	ENSP00000436682.1	P0C7Q2
	HTRA1-AS1	ENST00000647969.1		n.182+1614A>G		intron	N/A
	HTRA1-AS1	ENST00000650300.1		n.1852+1614A>G		intron	N/A

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

GnomAD2 exomes AF: 0.105 AC: 15831 AN: 150120 AF XY: 0.110

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 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

African (AFR) AF: 0.0342 AC: 1079 AN: 31524

American (AMR) AF: 0.0718 AC: 2552 AN: 35528

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 4371 AN: 25116

East Asian (EAS) AF: 0.00406 AC: 145 AN: 35724

South Asian (SAS) AF: 0.143 AC: 11206 AN: 78534

European-Finnish (FIN) AF: 0.0847 AC: 4167 AN: 49210

Middle Eastern (MID) AF: 0.179 AC: 1014 AN: 5670

European-Non Finnish (NFE) AF: 0.124 AC: 133039 AN: 1074312

Other (OTH) AF: 0.114 AC: 6566 AN: 57832

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

African (AFR) AF: 0.0366 AC: 1514 AN: 41412

American (AMR) AF: 0.0943 AC: 1441 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3468

East Asian (EAS) AF: 0.00676 AC: 35 AN: 5180

South Asian (SAS) AF: 0.149 AC: 718 AN: 4820

European-Finnish (FIN) AF: 0.0718 AC: 760 AN: 10586

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8561 AN: 68012

Other (OTH) AF: 0.109 AC: 229 AN: 2110

Alfa AF: 0.107 Hom.: 1475

Bravo AF: 0.0880

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.65
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs36213074; hg19: chr10-124216397;