rs727005

Variant names:

• chr1-35815735-A-G
• rs727005
• NM_017629.4:c.20-1147A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AGO4	NM_017629.4	c.20-1147A>G		intron_variant	Intron 1 of 17	ENST00000373210.4	NP_060099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO4	ENST00000373210.4	c.20-1147A>G		intron_variant	Intron 1 of 17	1	NM_017629.4	ENSP00000362306.3

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

African (AFR) AF: 0.322 AC: 13342 AN: 41462

American (AMR) AF: 0.312 AC: 4760 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3464

East Asian (EAS) AF: 0.705 AC: 3650 AN: 5178

South Asian (SAS) AF: 0.154 AC: 742 AN: 4822

European-Finnish (FIN) AF: 0.122 AC: 1292 AN: 10598

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0790 AC: 5375 AN: 68002

Other (OTH) AF: 0.193 AC: 406 AN: 2106

Alfa AF: 0.134 Hom.: 5700

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
PhyloP100		-0.0020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs727005; hg19: chr1-36281336;