rs243491

Positions:

• chr7-148749081-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CUL1	NM_003592.3	c.141-4895G>A		intron_variant		ENST00000325222.9	NP_003583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL1	ENST00000325222.9	c.141-4895G>A		intron_variant		1	NM_003592.3	ENSP00000326804	P1

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

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.591

Alfa AF: 0.543 Hom.: 4664

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

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: rs243491; hg19: chr7-148446173;