18-649311-A-G

Variant names:

• chr18-649311-A-G
• rs9966612
• NM_001393344.1:c.1398-587A>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.1398-587A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 152,036 control chromosomes in the GnomAD database, including 38,001 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 0.71 (38001 hom., cov: 31)
• Consequence: CLUL1 NM_001393344.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 15 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393344.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLUL1	NM_001393344.1	MANE Select	c.1398-587A>G		intron	N/A	NP_001380273.1
	CLUL1	NM_001289036.3		c.1398-587A>G		intron	N/A	NP_001275965.2
	CLUL1	NM_001318522.2		c.1398-587A>G		intron	N/A	NP_001305451.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLUL1	ENST00000692774.1	MANE Select	c.1398-587A>G		intron	N/A	ENSP00000510271.1
	CLUL1	ENST00000338387.11	TSL:1	c.1398-587A>G		intron	N/A	ENSP00000341128.6
	CLUL1	ENST00000400606.6	TSL:1	c.1398-587A>G		intron	N/A	ENSP00000383449.2

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107276 AN: 151918 Hom.: 37960 Cov.: 31

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.706 AC: 107381 AN: 152036 Hom.: 38001 Cov.: 31 AF XY: 0.703 AC XY: 52269 AN XY: 74324

African (AFR) AF: 0.731 AC: 30307 AN: 41462

American (AMR) AF: 0.662 AC: 10116 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2436 AN: 3468

East Asian (EAS) AF: 0.574 AC: 2966 AN: 5164

South Asian (SAS) AF: 0.651 AC: 3134 AN: 4812

European-Finnish (FIN) AF: 0.736 AC: 7779 AN: 10574

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48493 AN: 67970

Other (OTH) AF: 0.691 AC: 1459 AN: 2110

Alfa AF: 0.704 Hom.: 77030

Bravo AF: 0.702

Asia WGS AF: 0.624 AC: 2169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	14
DANN	Benign	0.68
PhyloP100		1.1
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: rs9966612; hg19: chr18-649311;