chr7-148773068-C-G

Variant names:

• chr7-148773068-C-G
• rs740951
• NM_003592.3:c.1083+5319C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003592.3(CUL1):​c.1083+5319C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003592.3. 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
	CUL1	NM_003592.3	MANE Select	c.1083+5319C>G		intron	N/A	NP_003583.2
	CUL1	NM_001370660.1		c.1083+5319C>G		intron	N/A	NP_001357589.1
	CUL1	NM_001370661.1		c.1083+5319C>G		intron	N/A	NP_001357590.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL1	ENST00000325222.9	TSL:1 MANE Select	c.1083+5319C>G		intron	N/A	ENSP00000326804.3
	CUL1	ENST00000409469.5	TSL:1	c.1083+5319C>G		intron	N/A	ENSP00000387160.1
	CUL1	ENST00000602748.5	TSL:5	c.1083+5319C>G		intron	N/A	ENSP00000473318.1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.76
DANN	Benign	0.53
PhyloP100		-0.36

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;