NM_001831.4:c.934+713G>C

Variant names:

• chr8-27603578-C-G
• rs9331926
• NM_001831.4:c.934+713G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001831.4(CLU):​c.934+713G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 152,260 control chromosomes in the GnomAD database, including 75 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 0.031 (75 hom., cov: 32)
• Consequence: CLU NM_001831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707
• Publications: 3 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=-0.8).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.031 (4718/152260) while in subpopulation AFR AF = 0.0328 (1362/41540). AF 95% confidence interval is 0.0313. There are 75 homozygotes in GnomAd4. There are 2370 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4718 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLU	NM_001831.4	c.934+713G>C		intron_variant	Intron 6 of 8	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.1189+713G>C		intron_variant	Intron 6 of 8
CLU	NR_045494.1	n.1114+713G>C		intron_variant	Intron 6 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.934+713G>C		intron_variant	Intron 6 of 8	1	NM_001831.4	ENSP00000315130.10

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 4713 AN: 152142 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0302

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0316

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0310 AC: 4718 AN: 152260 Hom.: 75 Cov.: 32 AF XY: 0.0318 AC XY: 2370 AN XY: 74436

African (AFR) AF: 0.0328 AC: 1362 AN: 41540

American (AMR) AF: 0.0301 AC: 461 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00705 AC: 34 AN: 4822

European-Finnish (FIN) AF: 0.0499 AC: 529 AN: 10608

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0316 AC: 2147 AN: 68020

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0317 Hom.: 13

Bravo AF: 0.0303

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.60
DANN	Benign	0.33
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism

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: rs9331926; hg19: chr8-27461095;