Variant 7-101916233-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_181552.4(CUX1):c.141+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 1,563,538 control chromosomes in the GnomAD database, including 3,863 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.047 ( 226 hom., cov: 32)

Exomes 𝑓: 0.067 ( 3637 hom. )

Consequence

CUX1
NM_181552.4 splice_region, intron

Scores

Splicing: ADA: 0.0003162

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.47

Variant links:

Genes affected

CUX1 (HGNC:2557): (cut like homeobox 1) The protein encoded by this gene is a member of the homeodomain family of DNA binding proteins. It may regulate gene expression, morphogenesis, and differentiation and it may also play a role in the cell cycle progession. Several alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Feb 2011]

CUX1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-101916233-G-A is Benign according to our data. Variant chr7-101916233-G-A is described in ClinVar as [Benign]. Clinvar id is 3060457.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX1	NM_001913.5 linkuse as main transcript	c.174+8G>A		splice_region_variant, intron_variant		ENST00000622516.6
CUX1	NM_181552.4 linkuse as main transcript	c.141+8G>A		splice_region_variant, intron_variant		ENST00000292535.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX1	ENST00000292535.12 linkuse as main transcript	c.141+8G>A		splice_region_variant, intron_variant		1	NM_181552.4	A2	P39880-1
CUX1	ENST00000622516.6 linkuse as main transcript	c.174+8G>A		splice_region_variant, intron_variant		1	NM_001913.5		Q13948-1

Frequencies

GnomAD3 genomes

AF:

0.0465

AC:

7075

AN:

152044

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0333

Gnomad ASJ

AF:

0.0582

Gnomad EAS

AF:

0.000967

Gnomad SAS

AF:

0.0447

Gnomad FIN

AF:

0.0604

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0719

Gnomad OTH

AF:

0.0422

GnomAD3 exomes

AF:

0.0528

AC:

13276

AN:

251380

Hom.:

473

AF XY:

0.0532

AC XY:

7230

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0121

Gnomad AMR exome

AF:

0.0459

Gnomad ASJ exome

AF:

0.0557

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0486

Gnomad FIN exome

AF:

0.0618

Gnomad NFE exome

AF:

0.0686

Gnomad OTH exome

AF:

0.0491

GnomAD4 exome

AF:

0.0666

AC:

93972

AN:

1411376

Hom.:

3637

Cov.:

AF XY:

0.0657

AC XY:

46350

AN XY:

705168

show subpopulations

Gnomad4 AFR exome

AF:

0.0107

Gnomad4 AMR exome

AF:

0.0449

Gnomad4 ASJ exome

AF:

0.0575

Gnomad4 EAS exome

AF:

0.000482

Gnomad4 SAS exome

AF:

0.0498

Gnomad4 FIN exome

AF:

0.0619

Gnomad4 NFE exome

AF:

0.0742

Gnomad4 OTH exome

AF:

0.0567

GnomAD4 genome

AF:

0.0465

AC:

7078

AN:

152162

Hom.:

226

Cov.:

AF XY:

0.0436

AC XY:

3243

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0125

Gnomad4 AMR

AF:

0.0332

Gnomad4 ASJ

AF:

0.0582

Gnomad4 EAS

AF:

0.000969

Gnomad4 SAS

AF:

0.0452

Gnomad4 FIN

AF:

0.0604

Gnomad4 NFE

AF:

0.0719

Gnomad4 OTH

AF:

0.0418

Alfa

AF:

0.0614

Hom.:

183

Bravo

AF:

0.0426

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CUX1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 04, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.2

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00032

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.040

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