8-27597058-C-T

Variant names:

• chr8-27597058-C-T
• rs10503814
• NM_001831.4:c.*1183G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001831.4(CLU):​c.*1183G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 454,004 control chromosomes in the GnomAD database, including 791 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 0.066 (522 hom., cov: 32)
  • Exomes 𝑓: 0.035 (269 hom.)
• Consequence: CLU NM_001831.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLU	NM_001831.4	c.*1183G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.2788G>A		non_coding_transcript_exon_variant	Exon 9 of 9
CLU	NR_045494.1	n.2713G>A		non_coding_transcript_exon_variant	Exon 9 of 9
LOC124901919	XR_007060868.1	n.1398-9C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403	c.*1183G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_001831.4	ENSP00000315130.10

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9968 AN: 152094 Hom.: 522 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0474

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0411

Gnomad OTH AF: 0.0603

GnomAD3 exomes AF: 0.0354 AC: 4622 AN: 130548 Hom.: 124 AF XY: 0.0332 AC XY: 2369 AN XY: 71256

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.0320

Gnomad ASJ exome AF: 0.0257

Gnomad EAS exome AF: 0.00949

Gnomad SAS exome AF: 0.0138

Gnomad FIN exome AF: 0.0210

Gnomad NFE exome AF: 0.0424

Gnomad OTH exome AF: 0.0367

GnomAD4 exome AF: 0.0349 AC: 10544 AN: 301792 Hom.: 269 Cov.: 0 AF XY: 0.0324 AC XY: 5575 AN XY: 171994

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0322

Gnomad4 ASJ exome AF: 0.0253

Gnomad4 EAS exome AF: 0.00988

Gnomad4 SAS exome AF: 0.0156

Gnomad4 FIN exome AF: 0.0202

Gnomad4 NFE exome AF: 0.0401

Gnomad4 OTH exome AF: 0.0395

GnomAD4 genome AF: 0.0656 AC: 9982 AN: 152212 Hom.: 522 Cov.: 32 AF XY: 0.0630 AC XY: 4691 AN XY: 74426

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0474

Gnomad4 ASJ AF: 0.0253

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.0175

Gnomad4 NFE AF: 0.0411

Gnomad4 OTH AF: 0.0597

Alfa AF: 0.0446 Hom.: 397

Bravo AF: 0.0713

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.5
DANN	Benign	0.66

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: rs10503814; hg19: chr8-27454575;