rs7920095

Variant names:

• chr10-35014406-G-A
• rs7920095
• NM_003591.4:c.1888-606C>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.1888-606C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,112 control chromosomes in the GnomAD database, including 7,063 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 0.29 (7063 hom., cov: 32)
• Consequence: CUL2 NM_003591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003591.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL2	NM_003591.4	MANE Select	c.1888-606C>T		intron	N/A	NP_003582.2
	CUL2	NM_001198778.2		c.1945-606C>T		intron	N/A	NP_001185707.1
	CUL2	NM_001198779.1		c.1927-606C>T		intron	N/A	NP_001185708.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL2	ENST00000374749.8	TSL:1 MANE Select	c.1888-606C>T		intron	N/A	ENSP00000363881.3
	CUL2	ENST00000374751.7	TSL:1	c.1888-606C>T		intron	N/A	ENSP00000363883.3
	CUL2	ENST00000688705.1		n.831C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44513 AN: 151994 Hom.: 7051 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.293 AC: 44561 AN: 152112 Hom.: 7063 Cov.: 32 AF XY: 0.295 AC XY: 21966 AN XY: 74352

African (AFR) AF: 0.163 AC: 6758 AN: 41526

American (AMR) AF: 0.299 AC: 4567 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1382 AN: 3464

East Asian (EAS) AF: 0.295 AC: 1526 AN: 5178

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

European-Finnish (FIN) AF: 0.390 AC: 4115 AN: 10548

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23536 AN: 67992

Other (OTH) AF: 0.323 AC: 682 AN: 2110

Alfa AF: 0.325 Hom.: 4580

Bravo AF: 0.279

Asia WGS AF: 0.342 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.70
DANN	Benign	0.21
PhyloP100		-0.60
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: rs7920095; hg19: chr10-35303334;