rs7099036

Variant names:

• chr10-35060646-C-T
• rs7099036
• NM_003591.4:c.317+228G>A

Variant summary

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

The NM_003591.4(CUL2):​c.317+228G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,028 control chromosomes in the GnomAD database, including 8,637 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 (8637 hom., cov: 32)
• Consequence: CUL2 NM_003591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL2	NM_003591.4	MANE Select	c.317+228G>A		intron	N/A	NP_003582.2
	CUL2	NM_001198778.2		c.374+228G>A		intron	N/A	NP_001185707.1	Q13617-2
	CUL2	NM_001198779.1		c.356+228G>A		intron	N/A	NP_001185708.1	Q13617

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL2	ENST00000374749.8	TSL:1 MANE Select	c.317+228G>A		intron	N/A	ENSP00000363881.3	Q13617-1
	CUL2	ENST00000374751.7	TSL:1	c.317+228G>A		intron	N/A	ENSP00000363883.3	Q13617-1
	CUL2	ENST00000970364.1		c.317+228G>A		intron	N/A	ENSP00000640423.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51066 AN: 151910 Hom.: 8613 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.336 AC: 51145 AN: 152028 Hom.: 8637 Cov.: 32 AF XY: 0.337 AC XY: 25077 AN XY: 74314

African (AFR) AF: 0.314 AC: 13019 AN: 41442

American (AMR) AF: 0.313 AC: 4791 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1352 AN: 3470

East Asian (EAS) AF: 0.295 AC: 1529 AN: 5176

South Asian (SAS) AF: 0.348 AC: 1679 AN: 4820

European-Finnish (FIN) AF: 0.391 AC: 4129 AN: 10554

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

European-Non Finnish (NFE) AF: 0.347 AC: 23577 AN: 67968

Other (OTH) AF: 0.351 AC: 739 AN: 2108

Alfa AF: 0.341 Hom.: 14777

Bravo AF: 0.328

Asia WGS AF: 0.351 AC: 1220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.60
PhyloP100		-0.69
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: rs7099036; hg19: chr10-35349574; COSMIC: COSV66081422; COSMIC: COSV66081422;