rs3750846

chr10-122456049-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMS2	NM_001099667.3	c.298-858T>C		intron_variant		ENST00000528446.1
LOC105378525	XR_946382.3	n.1874+2446A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMS2	ENST00000528446.1	c.298-858T>C		intron_variant		1	NM_001099667.3	P1
	ENST00000650300.1	n.1852+2446A>G		intron_variant, non_coding_transcript_variant
	ENST00000647969.1	n.182+2446A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.235

Alfa AF: 0.250 Hom.: 770

Bravo AF: 0.241

Asia WGS AF: 0.374 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.1
Dann	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs3750846; hg19: chr10-124215565;