1-35914532-T-C

Position:

• chr1-35914532-T-C

Variant summary

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

The NM_012199.5(AGO1):​c.1833+258T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,126 control chromosomes in the GnomAD database, including 13,403 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 0.34 (13403 hom., cov: 32)
• Consequence: AGO1 NM_012199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGO1	NM_012199.5	c.1833+258T>C		intron_variant		ENST00000373204.6	NP_036331.1
AGO1	NM_001317122.2	c.1833+258T>C		intron_variant			NP_001304051.1
AGO1	NM_001317123.2	c.1608+258T>C		intron_variant			NP_001304052.1
AGO1	XM_011541236.3	c.1842+258T>C		intron_variant			XP_011539538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGO1	ENST00000373204.6	c.1833+258T>C		intron_variant		1	NM_012199.5	ENSP00000362300.4

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51725 AN: 152008 Hom.: 13360 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.341 AC: 51836 AN: 152126 Hom.: 13403 Cov.: 32 AF XY: 0.346 AC XY: 25707 AN XY: 74376

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.314

Alfa AF: 0.167 Hom.: 3537

Bravo AF: 0.374

Asia WGS AF: 0.523 AC: 1813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.60

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: rs595055; hg19: chr1-36380133;