chr6-43040560-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014780.5(CUL7):c.3993G>A(p.Leu1331Leu) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. L1331L) has been classified as Likely 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

Publications

25 publications found

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:

KLC4 (HGNC:21624): (kinesin light chain 4) Predicted to be located in cytoplasm and microtubule. Predicted to be part of kinesin complex. [provided by Alliance of Genome Resources, Apr 2022]

KLC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 260441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
CUL7	NM_014780.5 link	c.3993G>A	p.Leu1331Leu	synonymous_variant	Exon 21 of 26	ENST00000265348.9	NP_055595.2	Q14999-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL7	ENST00000265348.9 link	c.3993G>A	p.Leu1331Leu	synonymous_variant	Exon 21 of 26	1	NM_014780.5	ENSP00000265348.4		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

GnomAD2 exomes

AF:

0.193

AC:

48599

AN:

251378

AF XY:

0.185

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 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

African (AFR)

AF:

0.591

AC:

19793

AN:

33480

American (AMR)

AF:

0.218

AC:

9756

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

2846

AN:

26136

East Asian (EAS)

AF:

0.257

AC:

10219

AN:

39700

South Asian (SAS)

AF:

0.225

AC:

19424

AN:

86258

European-Finnish (FIN)

AF:

0.115

AC:

6119

AN:

53392

Middle Eastern (MID)

AF:

0.162

AC:

934

AN:

5768

European-Non Finnish (NFE)

AF:

0.136

AC:

150717

AN:

1111958

Other (OTH)

AF:

0.183

AC:

11080

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

12676

25352

38027

50703

63379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5852

11704

17556

23408

29260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.270

AC:

41127

AN:

152168

Hom.:

8444

Cov.:

AF XY:

0.267

AC XY:

19884

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.577

AC:

23944

AN:

41492

American (AMR)

AF:

0.217

AC:

3318

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

393

AN:

3470

East Asian (EAS)

AF:

0.255

AC:

1320

AN:

5170

South Asian (SAS)

AF:

0.249

AC:

1202

AN:

4824

European-Finnish (FIN)

AF:

0.111

AC:

1178

AN:

10612

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9133

AN:

67994

Other (OTH)

AF:

0.246

AC:

518

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1279

2558

3836

5115

6394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.181

Hom.:

6060

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

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

3M syndrome 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.80

PhyloP100

0.67

PromoterAI

-0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over