rs529629931

Variant names:

• chr18-627325-A-C
• rs529629931
• NM_001393344.1:c.652A>C

Your query was ambiguous. Multiple possible variants found:

• chr18-627325-A-C
• chr18-627325-A-G
• chr18-627325-A-T

Variant summary

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

The NM_001393344.1(CLUL1):​c.652A>C​(p.Ile218Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I218V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: CLUL1 NM_001393344.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72

Genes affected

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

LOC105371952 (HGNC:):

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=0.06698027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLUL1	NM_001393344.1	c.652A>C	p.Ile218Leu	missense_variant	Exon 6 of 10	ENST00000692774.1	NP_001380273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLUL1	ENST00000692774.1	c.652A>C	p.Ile218Leu	missense_variant	Exon 6 of 10		NM_001393344.1	ENSP00000510271.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249522 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135376

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.47
DEOGEN2	Benign	0.0017	T;T;.;T;T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.69
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.54	.;.;T;T;.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.067	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;.;.;.;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.22	N;N;.;.;N;.
REVEL	Benign	0.023
Sift	Benign	0.83	T;T;.;.;T;.
Sift4G	Benign	0.83	T;T;T;T;T;T
Polyphen		0.0010	B;B;.;B;B;B
Vest4		0.19
MutPred		0.64		.;Gain of disorder (P = 0.0633);.;Gain of disorder (P = 0.0633);.;.;
MVP		0.014
MPC		0.23
ClinPred		0.033	T
GERP RS		1.9
Varity_R		0.051
gMVP		0.13

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: rs529629931; hg19: chr18-627325;