8-27597360-A-G

Variant names:

• chr8-27597360-A-G
• rs9331947
• NM_001831.4:c.*881T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001831.4(CLU):​c.*881T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 454,178 control chromosomes in the GnomAD database, including 304 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 0.028 (101 hom., cov: 32)
  • Exomes 𝑓: 0.029 (203 hom.)
• Consequence: CLU NM_001831.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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]

LOC124901919 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0276 (4191/151954) while in subpopulation NFE AF= 0.0425 (2885/67926). AF 95% confidence interval is 0.0412. There are 101 homozygotes in gnomad4. There are 2035 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4191 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLU	NM_001831.4	c.*881T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.2486T>C		non_coding_transcript_exon_variant	Exon 9 of 9
CLU	NR_045494.1	n.2411T>C		non_coding_transcript_exon_variant	Exon 9 of 9
LOC124901919	XR_007060868.1	n.1691A>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403	c.*881T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_001831.4	ENSP00000315130.10

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 4192 AN: 151832 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.00742

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00442

Gnomad FIN AF: 0.0490

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0425

Gnomad OTH AF: 0.0254

GnomAD3 exomes AF: 0.0241 AC: 3290 AN: 136660 Hom.: 71 AF XY: 0.0237 AC XY: 1758 AN XY: 74198

Gnomad AFR exome AF: 0.00544

Gnomad AMR exome AF: 0.0163

Gnomad ASJ exome AF: 0.0140

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00422

Gnomad FIN exome AF: 0.0494

Gnomad NFE exome AF: 0.0411

Gnomad OTH exome AF: 0.0290

GnomAD4 exome AF: 0.0291 AC: 8794 AN: 302224 Hom.: 203 Cov.: 0 AF XY: 0.0266 AC XY: 4589 AN XY: 172254

Gnomad4 AFR exome AF: 0.00713

Gnomad4 AMR exome AF: 0.0165

Gnomad4 ASJ exome AF: 0.0146

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00484

Gnomad4 FIN exome AF: 0.0465

Gnomad4 NFE exome AF: 0.0428

Gnomad4 OTH exome AF: 0.0303

GnomAD4 genome AF: 0.0276 AC: 4191 AN: 151954 Hom.: 101 Cov.: 32 AF XY: 0.0274 AC XY: 2035 AN XY: 74294

Gnomad4 AFR AF: 0.00740

Gnomad4 AMR AF: 0.0197

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00464

Gnomad4 FIN AF: 0.0490

Gnomad4 NFE AF: 0.0425

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0333 Hom.: 112

Bravo AF: 0.0246

Asia WGS AF: 0.00318 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.88
DANN	Benign	0.69

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: rs9331947; hg19: chr8-27454877;