rs727005

Positions:

• chr1-35815735-A-G

Variant summary

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

The NM_017629.4(AGO4):​c.20-1147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,098 control chromosomes in the GnomAD database, including 4,723 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 0.20 (4723 hom., cov: 31)
• Consequence: AGO4 NM_017629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

Genes affected

AGO4 (HGNC:18424): (argonaute RISC component 4) This gene encodes a member of the Argonaute family of proteins which contain PAZ and PIWI domains and play an integral role in RNA interference and short-interfering-RNA-mediated gene silencing. This gene is located on chromosome 1 in a cluster of related family members. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGO4	NM_017629.4	c.20-1147A>G		intron_variant		ENST00000373210.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGO4	ENST00000373210.4	c.20-1147A>G		intron_variant		1	NM_017629.4	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30071 AN: 151978 Hom.: 4702 Cov.: 31

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0790

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.198 AC: 30144 AN: 152098 Hom.: 4723 Cov.: 31 AF XY: 0.206 AC XY: 15316 AN XY: 74354

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0790

Gnomad4 OTH AF: 0.193

Alfa AF: 0.113 Hom.: 2454

Bravo AF: 0.228

Asia WGS AF: 0.360 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.99
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: rs727005; hg19: chr1-36281336;