rs867230

Variant names:

• chr8-27610986-C-A
• rs867230
• ENST00000523500.5:c.-415G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-27610986-C-A
• chr8-27610986-C-G
• chr8-27610986-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523500.5(CLU):​c.-415G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 359,682 control chromosomes in the GnomAD database, including 70,504 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 0.63 (29976 hom., cov: 32)
  • Exomes 𝑓: 0.62 (40528 hom.)
• Consequence: CLU ENST00000523500.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000523500.5. 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.-29-386G>T		intron	N/A	NP_001822.3
	CLU	NR_038335.2		n.226+160G>T		intron	N/A
	CLU	NR_045494.1		n.152-386G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLU	ENST00000523500.5	TSL:1	c.-415G>T		5_prime_UTR	Exon 1 of 8	ENSP00000429620.1	P10909-1
	CLU	ENST00000316403.15	TSL:1 MANE Select	c.-29-386G>T		intron	N/A	ENSP00000315130.10	P10909-1
	CLU	ENST00000405140.7	TSL:1	c.-30+160G>T		intron	N/A	ENSP00000385419.3	P10909-1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95188 AN: 151742 Hom.: 29955 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.627

GnomAD4 exome AF: 0.621 AC: 129074 AN: 207822 Hom.: 40528 Cov.: 0 AF XY: 0.628 AC XY: 71630 AN XY: 114122

African (AFR) AF: 0.655 AC: 3606 AN: 5504

American (AMR) AF: 0.655 AC: 7587 AN: 11590

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2768 AN: 4726

East Asian (EAS) AF: 0.762 AC: 6520 AN: 8562

South Asian (SAS) AF: 0.681 AC: 29041 AN: 42672

European-Finnish (FIN) AF: 0.593 AC: 5328 AN: 8992

Middle Eastern (MID) AF: 0.630 AC: 437 AN: 694

European-Non Finnish (NFE) AF: 0.588 AC: 67699 AN: 115040

Other (OTH) AF: 0.606 AC: 6088 AN: 10042

GnomAD4 genome AF: 0.627 AC: 95264 AN: 151860 Hom.: 29976 Cov.: 32 AF XY: 0.630 AC XY: 46767 AN XY: 74198

African (AFR) AF: 0.658 AC: 27261 AN: 41404

American (AMR) AF: 0.654 AC: 9991 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2007 AN: 3472

East Asian (EAS) AF: 0.772 AC: 3964 AN: 5138

South Asian (SAS) AF: 0.692 AC: 3333 AN: 4814

European-Finnish (FIN) AF: 0.601 AC: 6326 AN: 10520

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40311 AN: 67928

Other (OTH) AF: 0.630 AC: 1330 AN: 2112

Alfa AF: 0.616 Hom.: 14680

Bravo AF: 0.636

Asia WGS AF: 0.713 AC: 2477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.67
DANN	Benign	0.55
PhyloP100		-0.74
PromoterAI		0.027	Neutral
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)		0.010		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: rs867230; hg19: chr8-27468503;