Genetic Variant NM_181552.4:c.31-3032C>T (chr7-101913083-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181552.4(CUX1):c.31-3032C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 172,312 control chromosomes in the GnomAD database, including 8,095 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7410 hom., cov: 33)

Exomes 𝑓: 0.24 ( 685 hom. )

Consequence

CUX1
NM_181552.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.894

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

global developmental delay with or without impaired intellectual development
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CUX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUX1	NM_181552.4 link	c.31-3032C>T		intron_variant	Intron 1 of 23	ENST00000292535.12	NP_853530.2	P39880-1
CUX1	NM_001913.5 link	c.64-3032C>T		intron_variant	Intron 1 of 22	ENST00000622516.6	NP_001904.2	Q13948-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUX1	ENST00000292535.12 link	c.31-3032C>T		intron_variant	Intron 1 of 23	1	NM_181552.4	ENSP00000292535.7		P39880-1
CUX1	ENST00000622516.6 link	c.64-3032C>T		intron_variant	Intron 1 of 22	1	NM_001913.5	ENSP00000484760.2		Q13948-1

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45270

AN:

151998

Hom.:

7391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.296

GnomAD4 exome

AF:

0.236

AC:

4767

AN:

20194

Hom.:

685

Cov.:

AF XY:

0.237

AC XY:

2781

AN XY:

11740

show subpopulations

African (AFR)

AF:

0.424

AC:

162

AN:

382

American (AMR)

AF:

0.174

AC:

152

AN:

874

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

AN:

444

East Asian (EAS)

AF:

0.106

AC:

AN:

322

South Asian (SAS)

AF:

0.208

AC:

1074

AN:

5164

European-Finnish (FIN)

AF:

0.166

AC:

262

AN:

1582

Middle Eastern (MID)

AF:

0.276

AC:

AN:

European-Non Finnish (NFE)

AF:

0.261

AC:

2737

AN:

10498

Other (OTH)

AF:

0.269

AC:

234

AN:

870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

179

357

536

714

893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.298

AC:

45331

AN:

152118

Hom.:

7410

Cov.:

AF XY:

0.287

AC XY:

21322

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.416

AC:

17256

AN:

41482

American (AMR)

AF:

0.225

AC:

3431

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

970

AN:

3472

East Asian (EAS)

AF:

0.104

AC:

540

AN:

5186

South Asian (SAS)

AF:

0.193

AC:

930

AN:

4822

European-Finnish (FIN)

AF:

0.183

AC:

1936

AN:

10572

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.285

AC:

19380

AN:

67988

Other (OTH)

AF:

0.295

AC:

624

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1664

3329

4993

6658

8322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.279

Hom.:

12895

Bravo

AF:

0.307

Asia WGS

AF:

0.180

AC:

628

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.099

(source)

DANN

Benign

0.86

PhyloP100

-0.89

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

Computational scores

Splicing

Publications

Other links and lift over