chr1-35891011-G-T

Position:

• chr1-35891011-G-T

Variant summary

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

The NM_012199.5(AGO1):​c.210-1546G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 152,218 control chromosomes in the GnomAD database, including 2,030 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 0.087 (2030 hom., cov: 32)
• Consequence: AGO1 NM_012199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762

Genes affected

AGO1 (HGNC:3262): (argonaute RISC component 1) This gene encodes a member of the argonaute family of proteins, which associate with small RNAs and have important roles in RNA interference (RNAi) and RNA silencing. This protein binds to microRNAs (miRNAs) or small interfering RNAs (siRNAs) and represses translation of mRNAs that are complementary to them. It is also involved in transcriptional gene silencing (TGS) of promoter regions that are complementary to bound short antigene RNAs (agRNAs), as well as in the degradation of miRNA-bound mRNA targets. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A recent study showed this gene to be an authentic stop codon readthrough target, and that its mRNA could give rise to an additional C-terminally extended isoform by use of an alternative in-frame translation termination codon. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGO1	NM_012199.5	c.210-1546G>T		intron_variant		ENST00000373204.6
AGO1	NM_001317122.2	c.210-1546G>T		intron_variant
AGO1	NM_001317123.2	c.-16-1546G>T		intron_variant
AGO1	XM_011541236.3	c.210-1546G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGO1	ENST00000373204.6	c.210-1546G>T		intron_variant		1	NM_012199.5	P1

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 13173 AN: 152100 Hom.: 2021 Cov.: 32

Gnomad AFR AF: 0.0994

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.0752

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00764

Gnomad OTH AF: 0.0889

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

GnomAD4 genome AF: 0.0868 AC: 13205 AN: 152218 Hom.: 2030 Cov.: 32 AF XY: 0.0955 AC XY: 7109 AN XY: 74422

Gnomad4 AFR AF: 0.0993

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.0230

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.0659

Gnomad4 FIN AF: 0.0752

Gnomad4 NFE AF: 0.00764

Gnomad4 OTH AF: 0.0899

Alfa AF: 0.0300 Hom.: 529

Bravo AF: 0.107

Asia WGS AF: 0.293 AC: 1017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.62

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: rs11263833; hg19: chr1-36356612;