NM_001831.4:c.247-478A>G

Variant names:

• chr8-27607002-T-C
• rs11136000
• NM_001831.4:c.247-478A>G

Variant summary

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

The NM_001831.4(CLU):​c.247-478A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,100 control chromosomes in the GnomAD database, including 25,240 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 0.57 (25240 hom., cov: 33)
• Consequence: CLU NM_001831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305
• Publications: 354 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLU	NM_001831.4	MANE Select	c.247-478A>G		intron	N/A	NP_001822.3
	CLU	NR_038335.2		n.502-478A>G		intron	N/A
	CLU	NR_045494.1		n.427-478A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLU	ENST00000316403.15	TSL:1 MANE Select	c.247-478A>G		intron	N/A	ENSP00000315130.10
	CLU	ENST00000405140.7	TSL:1	c.247-478A>G		intron	N/A	ENSP00000385419.3
	CLU	ENST00000523500.5	TSL:1	c.247-478A>G		intron	N/A	ENSP00000429620.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86673 AN: 151982 Hom.: 25227 Cov.: 33

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.570 AC: 86726 AN: 152100 Hom.: 25240 Cov.: 33 AF XY: 0.575 AC XY: 42756 AN XY: 74348

African (AFR) AF: 0.444 AC: 18404 AN: 41468

American (AMR) AF: 0.636 AC: 9721 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1990 AN: 3468

East Asian (EAS) AF: 0.776 AC: 4006 AN: 5162

South Asian (SAS) AF: 0.703 AC: 3387 AN: 4820

European-Finnish (FIN) AF: 0.594 AC: 6288 AN: 10592

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40934 AN: 67984

Other (OTH) AF: 0.589 AC: 1246 AN: 2116

Alfa AF: 0.599 Hom.: 119389

Bravo AF: 0.569

Asia WGS AF: 0.707 AC: 2457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.29
PhyloP100		-0.30
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: rs11136000; hg19: chr8-27464519;