7-148773068-C-A

Variant names:

• chr7-148773068-C-A
• rs740951
• NM_003592.3:c.1083+5319C>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.1083+5319C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,954 control chromosomes in the GnomAD database, including 32,250 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 0.65 (32250 hom., cov: 30)
• Consequence: CUL1 NM_003592.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL1	NM_003592.3	c.1083+5319C>A		intron_variant	Intron 9 of 21	ENST00000325222.9	NP_003583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL1	ENST00000325222.9	c.1083+5319C>A		intron_variant	Intron 9 of 21	1	NM_003592.3	ENSP00000326804.3

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98741 AN: 151836 Hom.: 32235 Cov.: 30

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.650 AC: 98804 AN: 151954 Hom.: 32250 Cov.: 30 AF XY: 0.648 AC XY: 48100 AN XY: 74276

African (AFR) AF: 0.623 AC: 25805 AN: 41414

American (AMR) AF: 0.722 AC: 11035 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2357 AN: 3468

East Asian (EAS) AF: 0.667 AC: 3452 AN: 5176

South Asian (SAS) AF: 0.609 AC: 2925 AN: 4802

European-Finnish (FIN) AF: 0.565 AC: 5948 AN: 10536

Middle Eastern (MID) AF: 0.700 AC: 203 AN: 290

European-Non Finnish (NFE) AF: 0.664 AC: 45145 AN: 67968

Other (OTH) AF: 0.664 AC: 1401 AN: 2110

Alfa AF: 0.643 Hom.: 3895

Bravo AF: 0.664

Asia WGS AF: 0.652 AC: 2269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.68
PhyloP100		-0.36
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: rs740951; hg19: chr7-148470160;