chr18-618032-G-A

Variant names:

• chr18-618032-G-A
• rs766168896
• NM_001393344.1:c.32G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001393344.1(CLUL1):​c.32G>A​(p.Cys11Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLUL1 NM_001393344.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503

Genes affected

CLUL1 (HGNC:2096): (clusterin like 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022131473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLUL1	NM_001393344.1	c.32G>A	p.Cys11Tyr	missense_variant	Exon 3 of 10	ENST00000692774.1	NP_001380273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLUL1	ENST00000692774.1	c.32G>A	p.Cys11Tyr	missense_variant	Exon 3 of 10		NM_001393344.1	ENSP00000510271.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74314

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.2
DANN	Benign	0.67
DEOGEN2	Benign	0.0022	.;T;T;.;T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.15	T;.;.;T;T;.;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.022	T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.1	.;N;.;.;.;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	2.5	.;N;N;.;.;N;.
REVEL	Benign	0.036
Sift	Benign	1.0	.;T;T;.;.;T;.
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.0	.;B;B;.;B;B;B
Vest4		0.21, 0.21, 0.21
MutPred		0.55		.;.;Loss of sheet (P = 0.0025);.;Loss of sheet (P = 0.0025);.;.;
MVP		0.040
MPC		0.38
ClinPred		0.053	T
GERP RS		0.42
Varity_R		0.042
gMVP		0.067

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: rs766168896; hg19: chr18-618032;