Variant 6-43041138-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

LOC124901318 (HGNC:):

LOC124901318 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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CUL7	NM_014780.5 linkuse as main transcript	c.3646-63T>C		intron_variant		ENST00000265348.9	NP_055595.2
LOC124901318	XR_007059581.1 linkuse as main transcript	n.89+14A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL7	ENST00000265348.9 linkuse as main transcript	c.3646-63T>C		intron_variant		1	NM_014780.5	ENSP00000265348	P3	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

Gnomad4 AFR exome

AF:

0.242

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.0351

Gnomad4 EAS exome

AF:

0.177

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.0492

Gnomad4 NFE exome

AF:

0.0438

Gnomad4 OTH exome

AF:

0.0773

GnomAD4 genome

AF:

0.111

AC:

16873

AN:

152104

Hom.:

1508

Cov.:

AF XY:

0.112

AC XY:

8350

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.0485

Gnomad4 NFE

AF:

0.0430

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0792

Hom.:

121

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.8

DANN

Benign

0.79

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