NM_001099667.3:c.298-858T>C

Variant names:

• chr10-122456049-T-C
• rs3750846
• NM_001099667.3:c.298-858T>C

Variant summary

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

The NM_001099667.3(ARMS2):​c.298-858T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,984 control chromosomes in the GnomAD database, including 4,523 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 (4523 hom., cov: 32)
• Consequence: ARMS2 NM_001099667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 60 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 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.298-858T>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.298-858T>C		intron	N/A	ENSP00000436682.1	P0C7Q2
	HTRA1-AS1	ENST00000647969.1		n.182+2446A>G		intron	N/A
	HTRA1-AS1	ENST00000650300.1		n.1852+2446A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36214 AN: 151866 Hom.: 4515 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.239 AC: 36259 AN: 151984 Hom.: 4523 Cov.: 32 AF XY: 0.241 AC XY: 17904 AN XY: 74286

African (AFR) AF: 0.243 AC: 10091 AN: 41472

American (AMR) AF: 0.233 AC: 3561 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2153 AN: 5148

South Asian (SAS) AF: 0.320 AC: 1535 AN: 4800

European-Finnish (FIN) AF: 0.235 AC: 2476 AN: 10556

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.219 AC: 14916 AN: 67956

Other (OTH) AF: 0.235 AC: 496 AN: 2110

Alfa AF: 0.245 Hom.: 901

Bravo AF: 0.241

Asia WGS AF: 0.374 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.73
PhyloP100		0.12
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: rs3750846; hg19: chr10-124215565;