XM_011516968.3:c.-117+4878G>T

Variant names:

• chr8-140637315-C-A
• rs4961280
• XM_011516968.3:c.-117+4878G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011516968.3(AGO2):​c.-117+4878G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,220 control chromosomes in the GnomAD database, including 2,457 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 0.16 (2456 hom., cov: 32)
  • Exomes 𝑓: 0.25 (1 hom.)
• Consequence: AGO2 XM_011516968.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 37 publications found

Genes affected

AGO2 (HGNC:3263): (argonaute RISC catalytic component 2) This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, and contains a PAZ domain and a PIWI domain. It may interact with dicer1 and play a role in short-interfering-RNA-mediated gene silencing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ERICD (HGNC:49404): (E2F1-regulated inhibitor of cell death)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000623655.2. 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
	ERICD	NR_170171.1		n.3081C>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERICD	ENST00000623655.2	TSL:6	n.1035C>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24328 AN: 152034 Hom.: 2446 Cov.: 32

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.250 AC: 17 AN: 68 Hom.: 1 Cov.: 0 AF XY: 0.229 AC XY: 11 AN XY: 48

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.292 AC: 7 AN: 24

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 6 AN: 30

Other (OTH) AF: 0.375 AC: 3 AN: 8

GnomAD4 genome AF: 0.160 AC: 24337 AN: 152152 Hom.: 2456 Cov.: 32 AF XY: 0.164 AC XY: 12190 AN XY: 74376

African (AFR) AF: 0.0539 AC: 2239 AN: 41522

American (AMR) AF: 0.309 AC: 4716 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3468

East Asian (EAS) AF: 0.112 AC: 578 AN: 5178

South Asian (SAS) AF: 0.224 AC: 1076 AN: 4806

European-Finnish (FIN) AF: 0.185 AC: 1961 AN: 10580

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12498 AN: 67998

Other (OTH) AF: 0.163 AC: 344 AN: 2108

Alfa AF: 0.0627 Hom.: 78

Bravo AF: 0.161

Asia WGS AF: 0.170 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.061
DANN	Benign	0.48
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4961280; hg19: chr8-141647414;