NM_001099667.3:c.298-14_298-13insG

Variant names:

• chr10-122456893-T-TG
• rs529644268
• NM_001099667.3:c.298-14_298-13insG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001099667.3(ARMS2):​c.298-14_298-13insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,542,698 control chromosomes in the GnomAD database, including 60 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (29 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (31 hom.)
• Consequence: ARMS2 NM_001099667.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.213
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 10-122456893-T-TG is Benign according to our data. Variant chr10-122456893-T-TG is described in ClinVar as Likely_benign. ClinVar VariationId is 299030.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0118 (1802/152134) while in subpopulation AFR AF = 0.0397 (1645/41460). AF 95% confidence interval is 0.0381. There are 29 homozygotes in GnomAd4. There are 849 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

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.298-14_298-13insG		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.298-14_298-13insG		intron	N/A	ENSP00000436682.1	P0C7Q2
	HTRA1-AS1	ENST00000647969.1		n.182+1601_182+1602insC		intron	N/A
	HTRA1-AS1	ENST00000650300.1		n.1852+1601_1852+1602insC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1796 AN: 152016 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00577

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00748

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00814

GnomAD2 exomes AF: 0.00347 AC: 521 AN: 150120 AF XY: 0.00358

Gnomad AFR exome AF: 0.0368

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00191 AC: 2657 AN: 1390564 Hom.: 31 Cov.: 33 AF XY: 0.00201 AC XY: 1379 AN XY: 685728

African (AFR) AF: 0.0428 AC: 1343 AN: 31398

American (AMR) AF: 0.00285 AC: 101 AN: 35430

Ashkenazi Jewish (ASJ) AF: 0.0000402 AC: 1 AN: 24860

East Asian (EAS) AF: 0.00 AC: 0 AN: 35722

South Asian (SAS) AF: 0.00822 AC: 643 AN: 78236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49084

Middle Eastern (MID) AF: 0.00354 AC: 20 AN: 5642

European-Non Finnish (NFE) AF: 0.000296 AC: 318 AN: 1072646

Other (OTH) AF: 0.00401 AC: 231 AN: 57546

GnomAD4 genome AF: 0.0118 AC: 1802 AN: 152134 Hom.: 29 Cov.: 32 AF XY: 0.0114 AC XY: 849 AN XY: 74368

African (AFR) AF: 0.0397 AC: 1645 AN: 41460

American (AMR) AF: 0.00569 AC: 87 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00748 AC: 36 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68010

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.000863 Hom.: 0

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	Macular degeneration (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism

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: rs529644268; hg19: chr10-124216409;