1-35918014-ACTC-A

Variant names:

• chr1-35918014-ACTC-A
• rs368313581
• NM_012199.5:c.2163+293_2163+295delCCT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_012199.5(AGO1):​c.2163+293_2163+295delCCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 151,710 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0025 (3 hom., cov: 32)
• Consequence: AGO1 NM_012199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.926

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 385 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGO1	NM_012199.5	c.2163+293_2163+295delCCT		intron_variant	Intron 16 of 18	ENST00000373204.6	NP_036331.1
AGO1	NM_001317122.2	c.2163+293_2163+295delCCT		intron_variant	Intron 16 of 18		NP_001304051.1
AGO1	NM_001317123.2	c.1938+293_1938+295delCCT		intron_variant	Intron 16 of 18		NP_001304052.1
AGO1	XM_011541236.3	c.2172+293_2172+295delCCT		intron_variant	Intron 16 of 18		XP_011539538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO1	ENST00000373204.6	c.2163+293_2163+295delCCT		intron_variant	Intron 16 of 18	1	NM_012199.5	ENSP00000362300.4

Frequencies

GnomAD3 genomes AF: 0.00254 AC: 385 AN: 151592 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00881

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000920

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00240

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

GnomAD4 genome AF: 0.00254 AC: 385 AN: 151710 Hom.: 3 Cov.: 32 AF XY: 0.00251 AC XY: 186 AN XY: 74158

Gnomad4 AFR AF: 0.00878

Gnomad4 AMR AF: 0.000919

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.00238

Alfa AF: 0.00249 Hom.: 0

Bravo AF: 0.00259

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs368313581; hg19: chr1-36383615;