rs7923172

Variant names:

• chr10-35020439-G-A
• rs7923172
• NM_003591.4:c.1685-4045C>T

Variant summary

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

The NM_003591.4(CUL2):​c.1685-4045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,022 control chromosomes in the GnomAD database, including 8,638 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 0.34 (8638 hom., cov: 32)
• Consequence: CUL2 NM_003591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 12 publications found

Genes affected

CUL2 (HGNC:2552): (cullin 2) Enables ubiquitin protein ligase binding activity. Predicted to be involved in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process and protein ubiquitination. Predicted to act upstream of or within protein catabolic process. Located in nucleoplasm. Part of Cul2-RING 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL2	NM_003591.4	c.1685-4045C>T		intron_variant	Intron 17 of 20	ENST00000374749.8	NP_003582.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL2	ENST00000374749.8	c.1685-4045C>T		intron_variant	Intron 17 of 20	1	NM_003591.4	ENSP00000363881.3

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51080 AN: 151904 Hom.: 8614 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.337 AC: 51160 AN: 152022 Hom.: 8638 Cov.: 32 AF XY: 0.338 AC XY: 25086 AN XY: 74294

African (AFR) AF: 0.314 AC: 13007 AN: 41448

American (AMR) AF: 0.313 AC: 4783 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1385 AN: 3466

East Asian (EAS) AF: 0.296 AC: 1533 AN: 5184

South Asian (SAS) AF: 0.347 AC: 1671 AN: 4820

European-Finnish (FIN) AF: 0.391 AC: 4120 AN: 10544

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23592 AN: 67966

Other (OTH) AF: 0.350 AC: 739 AN: 2112

Alfa AF: 0.342 Hom.: 4882

Bravo AF: 0.328

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.31
PhyloP100		-0.27
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: rs7923172; hg19: chr10-35309367;