rs2273917

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014780.5(CUL7):c.3993G>A(p.Leu1331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,613,972 control chromosomes in the GnomAD database, including 31,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 8444 hom., cov: 32)

Exomes 𝑓: 0.16 ( 22705 hom. )

Consequence

CUL7
NM_014780.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.668

Variant links:

Genes affected

CUL7 (HGNC:21024): (cullin 7) The protein encoded by this gene is a component of an E3 ubiquitin-protein ligase complex. The encoded protein interacts with TP53, CUL9, and FBXW8 proteins. Defects in this gene are a cause of 3M syndrome type 1 (3M1). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

CUL7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 6-43040560-C-T is Benign according to our data. Variant chr6-43040560-C-T is described in ClinVar as [Benign]. Clinvar id is 260441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-43040560-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.668 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUL7	NM_014780.5 linkuse as main transcript	c.3993G>A	p.Leu1331=	synonymous_variant	21/26	ENST00000265348.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL7	ENST00000265348.9 linkuse as main transcript	c.3993G>A	p.Leu1331=	synonymous_variant	21/26	1	NM_014780.5	P3	Q14999-1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

41072

AN:

152050

Hom.:

8432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.577

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.242

GnomAD3 exomes

AF:

0.193

AC:

48599

AN:

251378

Hom.:

6514

AF XY:

0.185

AC XY:

25137

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.593

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.264

Gnomad SAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.158

AC:

230888

AN:

1461804

Hom.:

22705

Cov.:

AF XY:

0.158

AC XY:

114959

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.591

Gnomad4 AMR exome

AF:

0.218

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.136

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.270

AC:

41127

AN:

152168

Hom.:

8444

Cov.:

AF XY:

0.267

AC XY:

19884

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.577

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.255

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.246

Alfa

AF:

0.167

Hom.:

3997

Bravo

AF:

0.294

Asia WGS

AF:

0.290

AC:

1007

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.130

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

3M syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

Cadd

Benign

8.7

Dann

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over