rs1532277

Variant names:

• chr8-27608664-T-C
• rs1532277
• NM_001831.4:c.246+274A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-27608664-T-C
• chr8-27608664-T-G

Variant summary

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

The NM_001831.4(CLU):​c.246+274A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 564,874 control chromosomes in the GnomAD database, including 122,713 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 0.70 (38229 hom., cov: 34)
  • Exomes 𝑓: 0.64 (84484 hom.)
• Consequence: CLU NM_001831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLU	NM_001831.4	c.246+274A>G		intron_variant	Intron 3 of 8	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.501+274A>G		intron_variant	Intron 3 of 8
CLU	NR_045494.1	n.426+274A>G		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.246+274A>G		intron_variant	Intron 3 of 8	1	NM_001831.4	ENSP00000315130.10

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106184 AN: 152080 Hom.: 38174 Cov.: 34

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.687

GnomAD4 exome AF: 0.636 AC: 262257 AN: 412676 Hom.: 84484 Cov.: 3 AF XY: 0.638 AC XY: 139029 AN XY: 217966

Gnomad4 AFR exome AF: 0.882

Gnomad4 AMR exome AF: 0.679

Gnomad4 ASJ exome AF: 0.599

Gnomad4 EAS exome AF: 0.762

Gnomad4 SAS exome AF: 0.697

Gnomad4 FIN exome AF: 0.585

Gnomad4 NFE exome AF: 0.602

Gnomad4 OTH exome AF: 0.645

GnomAD4 genome AF: 0.698 AC: 106298 AN: 152198 Hom.: 38229 Cov.: 34 AF XY: 0.698 AC XY: 51948 AN XY: 74396

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.688

Alfa AF: 0.691 Hom.: 5329

Bravo AF: 0.716

Asia WGS AF: 0.744 AC: 2585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.41

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: rs1532277; hg19: chr8-27466181;