chr8-140612438-C-T

Position:

• chr8-140612438-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017014159.2(LOC107986982):​c.*9811G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,834 control chromosomes in the GnomAD database, including 7,569 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 0.31 (7569 hom., cov: 31)
• Consequence: LOC107986982 XM_017014159.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

Genes affected

LOC107986982 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC107986982	XM_017014159.2	c.*9811G>A		3_prime_UTR_variant	2/2
AGO2	NM_012154.5	c.22+23047G>A		intron_variant		ENST00000220592.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGO2	ENST00000220592.10	c.22+23047G>A		intron_variant		1	NM_012154.5	P1
AGO2	ENST00000519980.5	c.22+23047G>A		intron_variant		1
AGO2	ENST00000523609.5	c.22+23047G>A		intron_variant, NMD_transcript_variant		1
AGO2	ENST00000517293.5	n.62+23047G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47130 AN: 151716 Hom.: 7560 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.308

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.311 AC: 47167 AN: 151834 Hom.: 7569 Cov.: 31 AF XY: 0.310 AC XY: 22990 AN XY: 74212

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.307

Alfa AF: 0.289 Hom.: 13087

Bravo AF: 0.317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.54

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: rs2176397; hg19: chr8-141622537;