rs7812347

Positions:

• chr8-27602668-G-A

Variant summary

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

The NM_001831.4(CLU):​c.934+1623C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,538 control chromosomes in the GnomAD database, including 9,513 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 0.32 (9513 hom., cov: 31)
• Consequence: CLU NM_001831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLU	NM_001831.4	c.934+1623C>T		intron_variant		ENST00000316403.15
CLU	NR_038335.2	n.1189+1623C>T		intron_variant, non_coding_transcript_variant
CLU	NR_045494.1	n.1114+1623C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLU	ENST00000316403.15	c.934+1623C>T		intron_variant		1	NM_001831.4	P1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48388 AN: 151440 Hom.: 9490 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.320 AC: 48456 AN: 151538 Hom.: 9513 Cov.: 31 AF XY: 0.309 AC XY: 22853 AN XY: 73994

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.314

Alfa AF: 0.279 Hom.: 2097

Bravo AF: 0.337

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.70

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: rs7812347; hg19: chr8-27460185;