18-597751-T-G

Variant names:

• chr18-597751-T-G
• rs578026
• NM_001393344.1:c.-136+622T>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.-136+622T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,050 control chromosomes in the GnomAD database, including 5,654 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 0.25 (5654 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: CLUL1 NM_001393344.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.762
• Publications: 9 publications found

Genes affected

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLUL1	NM_001393344.1	MANE Select	c.-136+622T>G		intron	N/A	NP_001380273.1	Q15846
	CLUL1	NM_001289036.3		c.-259+622T>G		intron	N/A	NP_001275965.2	Q15846
	CLUL1	NM_001375492.2		c.-283+622T>G		intron	N/A	NP_001362421.1	Q15846

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLUL1	ENST00000692774.1	MANE Select	c.-136+622T>G		intron	N/A	ENSP00000510271.1	Q15846
	CLUL1	ENST00000400606.6	TSL:1	c.-14+622T>G		intron	N/A	ENSP00000383449.2	Q15846
	CLUL1	ENST00000581619.5	TSL:2	c.-845T>G		5_prime_UTR	Exon 1 of 8	ENSP00000463269.2	J3QKW8

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38750 AN: 151900 Hom.: 5648 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0490

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.125 AC: 4 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.115 AC XY: 3 AN XY: 26

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.125 AC: 3 AN: 24

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.255 AC: 38763 AN: 152018 Hom.: 5654 Cov.: 32 AF XY: 0.255 AC XY: 18924 AN XY: 74292

African (AFR) AF: 0.141 AC: 5850 AN: 41494

American (AMR) AF: 0.286 AC: 4363 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 821 AN: 3472

East Asian (EAS) AF: 0.0489 AC: 253 AN: 5172

South Asian (SAS) AF: 0.214 AC: 1029 AN: 4816

European-Finnish (FIN) AF: 0.355 AC: 3733 AN: 10526

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21757 AN: 67966

Other (OTH) AF: 0.255 AC: 538 AN: 2108

Alfa AF: 0.297 Hom.: 7538

Bravo AF: 0.245

Asia WGS AF: 0.122 AC: 427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.71
PhyloP100		0.76
PromoterAI		-0.00090	Neutral
Mutation Taster		=300/0	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: rs578026; hg19: chr18-597751;