Genetic Variant CUZD1:n.-307G>A (chr10-122846150-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 ENST00000338948.3(CUZD1):n.-307G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 285,780 control chromosomes in the GnomAD database, including 1,727 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 0.088 ( 806 hom., cov: 33)

Exomes 𝑓: 0.11 ( 921 hom. )

Consequence

CUZD1
ENST00000338948.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.449

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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM24B-CUZD1	NR_037915.1 link	n.370G>A		non_coding_transcript_exon_variant	Exon 3 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286088	ENST00000368904.6 link	n.-307G>A		non_coding_transcript_exon_variant	Exon 2 of 10	1		ENSP00000357900.2		A0A499FIG0
ENSG00000286088	ENST00000368904.6 link	n.-307G>A		5_prime_UTR_variant	Exon 2 of 10	1		ENSP00000357900.2		A0A499FIG0

Frequencies

GnomAD3 genomes

AF:

0.0884

AC:

13460

AN:

152192

Hom.:

808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.0648

Gnomad AMR

AF:

0.0977

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.0612

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.108

GnomAD4 exome

AF:

0.112

AC:

14951

AN:

133470

Hom.:

921

Cov.:

AF XY:

0.111

AC XY:

7576

AN XY:

68142

show subpopulations

African (AFR)

AF:

0.0315

AC:

135

AN:

4288

American (AMR)

AF:

0.126

AC:

551

AN:

4358

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

837

AN:

4856

East Asian (EAS)

AF:

0.000114

AC:

AN:

8766

South Asian (SAS)

AF:

0.0750

AC:

669

AN:

8916

European-Finnish (FIN)

AF:

0.130

AC:

983

AN:

7590

Middle Eastern (MID)

AF:

0.140

AC:

AN:

656

European-Non Finnish (NFE)

AF:

0.126

AC:

10700

AN:

85214

Other (OTH)

AF:

0.111

AC:

983

AN:

8826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

655

1310

1964

2619

3274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.0883

AC:

13454

AN:

152310

Hom.:

806

Cov.:

AF XY:

0.0880

AC XY:

6556

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0232

AC:

963

AN:

41568

American (AMR)

AF:

0.0979

AC:

1499

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

588

AN:

3472

East Asian (EAS)

AF:

0.000963

AC:

AN:

5190

South Asian (SAS)

AF:

0.0614

AC:

297

AN:

4834

European-Finnish (FIN)

AF:

0.134

AC:

1425

AN:

10604

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8350

AN:

68018

Other (OTH)

AF:

0.106

AC:

225

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

624

1248

1871

2495

3119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<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:

0.103

Hom.:

512

Bravo

AF:

0.0838

Asia WGS

AF:

0.0290

AC:

104

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

(source)

DANN

Benign

0.41

PhyloP100

0.45

PromoterAI

0.012

Neutral

(source)

Mutation Taster

=300/0

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