10-122456894-A-T

Variant names:

• chr10-122456894-A-T
• rs7088128
• NM_001099667.3:c.298-13A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001099667.3(ARMS2):​c.298-13A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,510,222 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (29 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (62 hom.)
• Consequence: ARMS2 NM_001099667.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.213
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-122456894-A-T is Benign according to our data. Variant chr10-122456894-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 299032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0119 (1804/151196) while in subpopulation AFR AF = 0.04 (1647/41158). AF 95% confidence interval is 0.0384. There are 29 homozygotes in GnomAd4. There are 850 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.298-13A>T		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.298-13A>T		intron	N/A	ENSP00000436682.1	P0C7Q2
	HTRA1-AS1	ENST00000647969.1		n.182+1601T>A		intron	N/A
	HTRA1-AS1	ENST00000650300.1		n.1852+1601T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1798 AN: 151076 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00753

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000207

Gnomad OTH AF: 0.00824

GnomAD2 exomes AF: 0.00386 AC: 538 AN: 139318 AF XY: 0.00398

Gnomad AFR exome AF: 0.0401

Gnomad AMR exome AF: 0.00215

Gnomad ASJ exome AF: 0.000126

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000355

Gnomad OTH exome AF: 0.00126

GnomAD4 exome AF: 0.00199 AC: 2708 AN: 1359026 Hom.: 62 Cov.: 33 AF XY: 0.00211 AC XY: 1417 AN XY: 670354

African (AFR) AF: 0.0456 AC: 1384 AN: 30318

American (AMR) AF: 0.00298 AC: 100 AN: 33598

Ashkenazi Jewish (ASJ) AF: 0.0000821 AC: 2 AN: 24360

East Asian (EAS) AF: 0.00 AC: 0 AN: 33764

South Asian (SAS) AF: 0.00866 AC: 660 AN: 76172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47930

Middle Eastern (MID) AF: 0.00358 AC: 20 AN: 5582

European-Non Finnish (NFE) AF: 0.000290 AC: 305 AN: 1051132

Other (OTH) AF: 0.00422 AC: 237 AN: 56170

GnomAD4 genome AF: 0.0119 AC: 1804 AN: 151196 Hom.: 29 Cov.: 32 AF XY: 0.0115 AC XY: 850 AN XY: 73798

African (AFR) AF: 0.0400 AC: 1647 AN: 41158

American (AMR) AF: 0.00575 AC: 87 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00753 AC: 36 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10430

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

European-Non Finnish (NFE) AF: 0.000207 AC: 14 AN: 67786

Other (OTH) AF: 0.00815 AC: 17 AN: 2086

Alfa AF: 0.000285 Hom.: 334

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Age related macular degeneration 8 (1)
-	-	1	Macular degeneration (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.70
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: rs7088128; hg19: chr10-124216410;