rs10488072

chr7-148721974-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003592.3(CUL1):c.-161-7988C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,108 control chromosomes in the GnomAD database, including 698 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 0.091 (698 hom., cov: 32)
• Consequence: CUL1 NM_003592.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUL1	NM_003592.3	c.-161-7988C>T		intron_variant		ENST00000325222.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL1	ENST00000325222.9	c.-161-7988C>T		intron_variant		1	NM_003592.3	P1

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13854 AN: 151990 Hom.: 688 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0453

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.0819

Gnomad EAS AF: 0.0912

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0743

Gnomad OTH AF: 0.0857

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

GnomAD4 genome AF: 0.0914 AC: 13898 AN: 152108 Hom.: 698 Cov.: 32 AF XY: 0.0938 AC XY: 6973 AN XY: 74344

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.0819

Gnomad4 EAS AF: 0.0918

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.0809

Gnomad4 NFE AF: 0.0743

Gnomad4 OTH AF: 0.0915

Alfa AF: 0.0780 Hom.: 533

Bravo AF: 0.0903

Asia WGS AF: 0.167 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.51
Dann	Benign	0.79

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: rs10488072; hg19: chr7-148419066;