rs7982

Positions:

• chr8-27604964-A-C
• chr8-27604964-A-G
• chr8-27604964-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001831.4(CLU):​c.789T>G​(p.His263Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLU NM_001831.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25799242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLU	NM_001831.4	c.789T>G	p.His263Gln	missense_variant	5/9	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.1044T>G		non_coding_transcript_exon_variant	5/9
CLU	NR_045494.1	n.969T>G		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.789T>G	p.His263Gln	missense_variant	5/9	1	NM_001831.4	ENSP00000315130	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.039
DANN	Benign	0.67
DEOGEN2	Benign	0.072	T;T;T;T;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.54	.;.;T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.83	L;L;L;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.38	N;N;N;N;N
REVEL	Benign	0.022
Sift	Benign	0.17	T;T;T;T;T
Sift4G	Benign	0.45	T;T;T;T;.
Polyphen		0.010	B;B;B;.;.
Vest4		0.16
MutPred		0.69		Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);.;.;
MVP		0.43
MPC		0.52
ClinPred		0.048	T
GERP RS		-0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.028
gMVP		0.27

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: rs7982; hg19: chr8-27462481;