Genetic Variant CUZD1:c.1382+69T>C (chr10-122834637-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_022034.6(CUZD1):c.1382+69T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,330,384 control chromosomes in the GnomAD database, including 188,584 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 0.47 ( 17816 hom., cov: 32)

Exomes 𝑓: 0.53 ( 170768 hom. )

Consequence

CUZD1
NM_022034.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.16

Publications

4 publications found

Variant links:

Genes affected

CUZD1 (HGNC:17937): (CUB and zona pellucida like domains 1) Predicted to be involved in trypsinogen activation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CUZD1 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

CUZD1 links:

ENSG00000286088 (HGNC:):

ENSG00000286088 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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CUZD1	NM_022034.6 link	c.1382+69T>C	intron_variant	Intron 7 of 8	ENST00000392790.6	NP_071317.2	Q86UP6-1
CUZD1	NR_037912.2 link	n.1245+69T>C	intron_variant	Intron 6 of 7
FAM24B-CUZD1	NR_037915.1 link	n.2058+69T>C	intron_variant	Intron 9 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUZD1	ENST00000392790.6 link	c.1382+69T>C		intron_variant	Intron 7 of 8	1	NM_022034.6	ENSP00000376540.1		Q86UP6-1
ENSG00000286088	ENST00000368904.6 link	n.*543+69T>C		intron_variant	Intron 8 of 9	1		ENSP00000357900.2		A0A499FIG0

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70817

AN:

151812

Hom.:

17819

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.651

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.538

Gnomad EAS

AF:

0.501

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.625

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.489

GnomAD4 exome

AF:

0.535

AC:

629949

AN:

1178456

Hom.:

170768

AF XY:

0.534

AC XY:

308723

AN XY:

578508

show subpopulations

African (AFR)

AF:

0.259

AC:

6846

AN:

26390

American (AMR)

AF:

0.473

AC:

11307

AN:

23912

Ashkenazi Jewish (ASJ)

AF:

0.537

AC:

9731

AN:

18126

East Asian (EAS)

AF:

0.506

AC:

18556

AN:

36644

South Asian (SAS)

AF:

0.479

AC:

24278

AN:

50682

European-Finnish (FIN)

AF:

0.613

AC:

28535

AN:

46574

Middle Eastern (MID)

AF:

0.435

AC:

2047

AN:

4710

European-Non Finnish (NFE)

AF:

0.546

AC:

503056

AN:

922144

Other (OTH)

AF:

0.519

AC:

25593

AN:

49274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

13925

27850

41775

55700

69625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14522

29044

43566

58088

72610

<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:

0.466

AC:

70828

AN:

151928

Hom.:

17816

Cov.:

AF XY:

0.469

AC XY:

34852

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.268

AC:

11126

AN:

41444

American (AMR)

AF:

0.493

AC:

7521

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.538

AC:

1868

AN:

3470

East Asian (EAS)

AF:

0.504

AC:

2605

AN:

5172

South Asian (SAS)

AF:

0.468

AC:

2256

AN:

4818

European-Finnish (FIN)

AF:

0.625

AC:

6591

AN:

10538

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.546

AC:

37097

AN:

67906

Other (OTH)

AF:

0.485

AC:

1024

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1827

3653

5480

7306

9133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.487

Hom.:

18388

Bravo

AF:

0.447

Asia WGS

AF:

0.472

AC:

1640

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.2

(source)

DANN

Benign

0.79

PhyloP100

3.2

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