NM_001099667.3:c.112C>T

Variant names:

• chr10-122454839-C-T
• rs2736911
• NM_001099667.3:c.112C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001099667.3(ARMS2):​c.112C>T​(p.Arg38*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,820 control chromosomes in the GnomAD database, including 18,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.13 (1497 hom., cov: 31)
  • Exomes 𝑓: 0.15 (16559 hom.)
• Consequence: ARMS2 NM_001099667.3 stop_gained
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.417
• Publications: 70 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 -16 ACMG points.

• BP6: Variant 10-122454839-C-T is Benign according to our data. Variant chr10-122454839-C-T is described in ClinVar as Benign. ClinVar VariationId is 299029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 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.112C>T	p.Arg38*	stop_gained	Exon 1 of 2	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.112C>T	p.Arg38*	stop_gained	Exon 1 of 2	ENSP00000436682.1	P0C7Q2
	HTRA1-AS1	ENST00000647969.1		n.182+3656G>A		intron	N/A
	HTRA1-AS1	ENST00000650300.1		n.1852+3656G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19959 AN: 152014 Hom.: 1494 Cov.: 31

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.131 AC: 32700 AN: 249226 AF XY: 0.130

Gnomad AFR exome AF: 0.0709

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.127

Gnomad EAS exome AF: 0.155

Gnomad FIN exome AF: 0.162

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.146 AC: 213900 AN: 1461688 Hom.: 16559 Cov.: 34 AF XY: 0.144 AC XY: 104970 AN XY: 727124

African (AFR) AF: 0.0705 AC: 2360 AN: 33480

American (AMR) AF: 0.111 AC: 4943 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3390 AN: 26136

East Asian (EAS) AF: 0.185 AC: 7328 AN: 39700

South Asian (SAS) AF: 0.0690 AC: 5954 AN: 86258

European-Finnish (FIN) AF: 0.162 AC: 8637 AN: 53402

Middle Eastern (MID) AF: 0.0669 AC: 386 AN: 5768

European-Non Finnish (NFE) AF: 0.155 AC: 172613 AN: 1111846

Other (OTH) AF: 0.137 AC: 8289 AN: 60374

GnomAD4 genome AF: 0.131 AC: 19976 AN: 152132 Hom.: 1497 Cov.: 31 AF XY: 0.130 AC XY: 9658 AN XY: 74376

African (AFR) AF: 0.0753 AC: 3126 AN: 41504

American (AMR) AF: 0.132 AC: 2017 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3472

East Asian (EAS) AF: 0.165 AC: 853 AN: 5164

South Asian (SAS) AF: 0.0680 AC: 328 AN: 4822

European-Finnish (FIN) AF: 0.171 AC: 1804 AN: 10572

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10959 AN: 67992

Other (OTH) AF: 0.136 AC: 287 AN: 2110

Alfa AF: 0.137 Hom.: 1667

Bravo AF: 0.125

TwinsUK AF: 0.150 AC: 557

ALSPAC AF: 0.158 AC: 608

ESP6500AA AF: 0.0709 AC: 288

ESP6500EA AF: 0.152 AC: 1274

ExAC AF: 0.131 AC: 15813

Asia WGS AF: 0.106 AC: 369 AN: 3478

EpiCase AF: 0.151

EpiControl AF: 0.147

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Age related macular degeneration 8 (1)
-	-	1	ARMS2-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Benign	0.95
Eigen	Benign	-0.63
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0040	N
PhyloP100		-0.42
Vest4		0.66
GERP RS		-2.2
PromoterAI		-0.028	Neutral
Mutation Taster		=192/8	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: rs2736911; hg19: chr10-124214355; COSMIC: COSV73306995;