chr8-27597169-T-C

Variant names:

• chr8-27597169-T-C
• rs9331949
• NM_001831.4:c.*1072A>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.*1072A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 454,130 control chromosomes in the GnomAD database, including 1,365 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 0.049 (334 hom., cov: 32)
  • Exomes 𝑓: 0.059 (1031 hom.)
• Consequence: CLU NM_001831.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 20 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]

ENSG00000300853 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 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.*1072A>G		3_prime_UTR	Exon 9 of 9	NP_001822.3
	CLU	NR_038335.2		n.2677A>G		non_coding_transcript_exon	Exon 9 of 9
	CLU	NR_045494.1		n.2602A>G		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLU	ENST00000316403.15	TSL:1 MANE Select	c.*1072A>G		3_prime_UTR	Exon 9 of 9	ENSP00000315130.10
	ENSG00000300853	ENST00000774578.1		n.272T>C		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000300853	ENST00000774579.1		n.387T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7522 AN: 152158 Hom.: 334 Cov.: 32

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0407

GnomAD2 exomes AF: 0.0617 AC: 8240 AN: 133564 AF XY: 0.0687

Gnomad AFR exome AF: 0.0702

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.0269

Gnomad EAS exome AF: 0.206

Gnomad FIN exome AF: 0.0703

Gnomad NFE exome AF: 0.0279

Gnomad OTH exome AF: 0.0370

GnomAD4 exome AF: 0.0586 AC: 17676 AN: 301854 Hom.: 1031 Cov.: 0 AF XY: 0.0675 AC XY: 11619 AN XY: 172034

African (AFR) AF: 0.0707 AC: 605 AN: 8554

American (AMR) AF: 0.0107 AC: 293 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.0293 AC: 316 AN: 10786

East Asian (EAS) AF: 0.207 AC: 1910 AN: 9210

South Asian (SAS) AF: 0.141 AC: 8437 AN: 59650

European-Finnish (FIN) AF: 0.0668 AC: 830 AN: 12424

Middle Eastern (MID) AF: 0.0243 AC: 28 AN: 1150

European-Non Finnish (NFE) AF: 0.0290 AC: 4607 AN: 158764

Other (OTH) AF: 0.0463 AC: 650 AN: 14042

GnomAD4 genome AF: 0.0494 AC: 7522 AN: 152276 Hom.: 334 Cov.: 32 AF XY: 0.0533 AC XY: 3966 AN XY: 74468

African (AFR) AF: 0.0620 AC: 2575 AN: 41560

American (AMR) AF: 0.0158 AC: 242 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1108 AN: 5176

South Asian (SAS) AF: 0.138 AC: 664 AN: 4818

European-Finnish (FIN) AF: 0.0754 AC: 800 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0268 AC: 1824 AN: 68028

Other (OTH) AF: 0.0398 AC: 84 AN: 2112

Alfa AF: 0.0303 Hom.: 128

Bravo AF: 0.0447

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	10
DANN	Benign	0.84
PhyloP100		0.28
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: rs9331949; hg19: chr8-27454686;