rs9331892

Variant names:

• chr8-27610488-G-A
• rs9331892
• NM_001831.4:c.84C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-27610488-G-A
• chr8-27610488-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001831.4(CLU):​c.84C>T​(p.Asp28Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,613,914 control chromosomes in the GnomAD database, including 1,541 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 0.055 (828 hom., cov: 33)
  • Exomes 𝑓: 0.0056 (713 hom.)
• Consequence: CLU NM_001831.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.907
• Publications: 4 publications found

Genes affected

CLU (HGNC:2095): (clusterin) The protein encoded by this gene is a secreted chaperone that can under some stress conditions also be found in the cell cytosol. It has been suggested to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders. Alternate splicing results in both coding and non-coding variants.[provided by RefSeq, May 2011]

MIR6843 (HGNC:50240): (microRNA 6843) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=0.907 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001831.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLU	NM_001831.4	MANE Select	c.84C>T	p.Asp28Asp	synonymous	Exon 2 of 9	NP_001822.3
	CLU	NR_038335.2		n.339C>T		non_coding_transcript_exon	Exon 2 of 9
	CLU	NR_045494.1		n.264C>T		non_coding_transcript_exon	Exon 2 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLU	ENST00000316403.15	TSL:1 MANE Select	c.84C>T	p.Asp28Asp	synonymous	Exon 2 of 9	ENSP00000315130.10	P10909-1
	CLU	ENST00000405140.7	TSL:1	c.84C>T	p.Asp28Asp	synonymous	Exon 2 of 9	ENSP00000385419.3	P10909-1
	CLU	ENST00000523500.5	TSL:1	c.84C>T	p.Asp28Asp	synonymous	Exon 1 of 8	ENSP00000429620.1	P10909-1

Frequencies

GnomAD3 genomes AF: 0.0551 AC: 8393 AN: 152208 Hom.: 828 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0406

GnomAD2 exomes AF: 0.0140 AC: 3528 AN: 251438 AF XY: 0.0102

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.00882

Gnomad ASJ exome AF: 0.00218

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000501

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00560 AC: 8184 AN: 1461588 Hom.: 713 Cov.: 31 AF XY: 0.00476 AC XY: 3460 AN XY: 727106

African (AFR) AF: 0.196 AC: 6543 AN: 33466

American (AMR) AF: 0.00964 AC: 431 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00264 AC: 69 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000417 AC: 36 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00937 AC: 54 AN: 5766

European-Non Finnish (NFE) AF: 0.000291 AC: 324 AN: 1111792

Other (OTH) AF: 0.0120 AC: 727 AN: 60374

GnomAD4 genome AF: 0.0552 AC: 8408 AN: 152326 Hom.: 828 Cov.: 33 AF XY: 0.0526 AC XY: 3915 AN XY: 74498

African (AFR) AF: 0.191 AC: 7947 AN: 41542

American (AMR) AF: 0.0202 AC: 309 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68032

Other (OTH) AF: 0.0402 AC: 85 AN: 2114

Alfa AF: 0.0259 Hom.: 187

Bravo AF: 0.0628

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.26
PhyloP100		0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9331892; hg19: chr8-27468005;