rs243491

Variant names:

• chr7-148749081-G-A
• rs243491
• NM_003592.3:c.141-4895G>A

Variant summary

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

The NM_003592.3(CUL1):​c.141-4895G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,958 control chromosomes in the GnomAD database, including 25,956 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 0.58 (25956 hom., cov: 31)
• Consequence: CUL1 NM_003592.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 2 publications found

Genes affected

CUL1 (HGNC:2551): (cullin 1) Predicted to enable ubiquitin protein ligase binding activity and ubiquitin-protein transferase activity. Involved in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process and protein ubiquitination. Located in plasma membrane. Part of Parkin-FBXW7-Cul1 ubiquitin ligase complex and SCF ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL1	NM_003592.3	c.141-4895G>A		intron_variant	Intron 2 of 21	ENST00000325222.9	NP_003583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL1	ENST00000325222.9	c.141-4895G>A		intron_variant	Intron 2 of 21	1	NM_003592.3	ENSP00000326804.3

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87912 AN: 151840 Hom.: 25904 Cov.: 31

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.579 AC: 88025 AN: 151958 Hom.: 25956 Cov.: 31 AF XY: 0.583 AC XY: 43343 AN XY: 74300

African (AFR) AF: 0.674 AC: 27942 AN: 41434

American (AMR) AF: 0.605 AC: 9238 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1851 AN: 3470

East Asian (EAS) AF: 0.550 AC: 2834 AN: 5152

South Asian (SAS) AF: 0.624 AC: 3003 AN: 4814

European-Finnish (FIN) AF: 0.576 AC: 6070 AN: 10544

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.518 AC: 35230 AN: 67970

Other (OTH) AF: 0.591 AC: 1241 AN: 2100

Alfa AF: 0.540 Hom.: 33365

Bravo AF: 0.585

Asia WGS AF: 0.628 AC: 2183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		0.071
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: rs243491; hg19: chr7-148446173;