Genetic Variant CUL7:c.3646-63T>C (chr6-43041138-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014780.5(CUL7):c.3646-63T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 1,550,338 control chromosomes in the GnomAD database, including 5,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1508 hom., cov: 32)

Exomes 𝑓: 0.062 ( 4265 hom. )

Consequence

CUL7
NM_014780.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0580

Publications

2 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:

LOC124901318 (HGNC:):

LOC124901318 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-43041138-A-G is Benign according to our data. Variant chr6-43041138-A-G is described in ClinVar as [Benign]. Clinvar id is 1260766.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL7	NM_014780.5 link	c.3646-63T>C		intron_variant	Intron 19 of 25	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.3646-63T>C		intron_variant	Intron 19 of 25	1	NM_014780.5	ENSP00000265348.4		Q14999-1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16850

AN:

151986

Hom.:

1503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.0485

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0430

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.0619

AC:

86534

AN:

1398234

Hom.:

4265

Cov.:

AF XY:

0.0626

AC XY:

43648

AN XY:

697262

show subpopulations

African (AFR)

AF:

0.242

AC:

7797

AN:

32204

American (AMR)

AF:

0.155

AC:

6685

AN:

43056

Ashkenazi Jewish (ASJ)

AF:

0.0351

AC:

898

AN:

25558

East Asian (EAS)

AF:

0.177

AC:

6872

AN:

38904

South Asian (SAS)

AF:

0.126

AC:

10533

AN:

83532

European-Finnish (FIN)

AF:

0.0492

AC:

2578

AN:

52366

Middle Eastern (MID)

AF:

0.0476

AC:

215

AN:

4516

European-Non Finnish (NFE)

AF:

0.0438

AC:

46468

AN:

1060058

Other (OTH)

AF:

0.0773

AC:

4488

AN:

58040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

4221

8442

12664

16885

21106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.111

AC:

16873

AN:

152104

Hom.:

1508

Cov.:

AF XY:

0.112

AC XY:

8350

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.226

AC:

9376

AN:

41460

American (AMR)

AF:

0.132

AC:

2022

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

130

AN:

3466

East Asian (EAS)

AF:

0.180

AC:

931

AN:

5170

South Asian (SAS)

AF:

0.149

AC:

719

AN:

4820

European-Finnish (FIN)

AF:

0.0485

AC:

514

AN:

10602

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0430

AC:

2922

AN:

67996

Other (OTH)

AF:

0.106

AC:

223

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

711

1422

2132

2843

3554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0842

Hom.:

133

Bravo

AF:

0.122

Asia WGS

AF:

0.189

AC:

657

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.8

(source)

DANN

Benign

0.79

PhyloP100

0.058

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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6-43041138-A-G

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