18-648465-A-G

Variant names:

• chr18-648465-A-G
• rs11877057
• NM_001393344.1:c.1398-1433A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393344.1(CLUL1):​c.1398-1433A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,162 control chromosomes in the GnomAD database, including 1,854 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 0.14 (1854 hom., cov: 32)
• Consequence: CLUL1 NM_001393344.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450
• Publications: 2 publications found

Genes affected

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

TYMSOS (HGNC:29553): (TYMS opposite strand RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLUL1	NM_001393344.1	c.1398-1433A>G		intron_variant	Intron 9 of 9	ENST00000692774.1	NP_001380273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLUL1	ENST00000692774.1	c.1398-1433A>G		intron_variant	Intron 9 of 9		NM_001393344.1	ENSP00000510271.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21319 AN: 152044 Hom.: 1855 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.140 AC: 21341 AN: 152162 Hom.: 1854 Cov.: 32 AF XY: 0.142 AC XY: 10569 AN XY: 74408

African (AFR) AF: 0.230 AC: 9563 AN: 41492

American (AMR) AF: 0.0807 AC: 1234 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3470

East Asian (EAS) AF: 0.257 AC: 1331 AN: 5174

South Asian (SAS) AF: 0.132 AC: 638 AN: 4822

European-Finnish (FIN) AF: 0.120 AC: 1268 AN: 10600

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0957 AC: 6509 AN: 68004

Other (OTH) AF: 0.115 AC: 242 AN: 2110

Alfa AF: 0.103 Hom.: 1130

Bravo AF: 0.142

Asia WGS AF: 0.188 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.51
PhyloP100		0.045
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11877057; hg19: chr18-648465;