10-122455799-T-G

Variant names:

• chr10-122455799-T-G
• rs3750848
• NM_001099667.3:c.297+775T>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+775T>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 151,984 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: 0.811
• Publications: 38 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMS2	NM_001099667.3	MANE Select	c.297+775T>G		intron	N/A	NP_001093137.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMS2	ENST00000528446.1	TSL:1 MANE Select	c.297+775T>G		intron	N/A	ENSP00000436682.1
	ENSG00000285955	ENST00000647969.1		n.182+2696A>C		intron	N/A
	ENSG00000285955	ENST00000650300.1		n.1852+2696A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35683 AN: 151866 Hom.: 4410 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.193

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: 35723 AN: 151984 Hom.: 4417 Cov.: 32 AF XY: 0.238 AC XY: 17653 AN XY: 74278

African (AFR) AF: 0.231 AC: 9593 AN: 41452

American (AMR) AF: 0.232 AC: 3549 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 705 AN: 3470

East Asian (EAS) AF: 0.415 AC: 2138 AN: 5146

South Asian (SAS) AF: 0.319 AC: 1525 AN: 4780

European-Finnish (FIN) AF: 0.234 AC: 2480 AN: 10580

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14917 AN: 67972

Other (OTH) AF: 0.233 AC: 492 AN: 2112

Alfa AF: 0.230 Hom.: 7895

Bravo AF: 0.237

Asia WGS AF: 0.369 AC: 1279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		0.81
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: rs3750848; hg19: chr10-124215315;