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 ENST00000368904.6(ENSG00000286088):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

ENSG00000286088
ENST00000368904.6 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

new If you want to explore the variant's impact on the transcript ENST00000368904.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368904.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM24B-CUZD1	NR_037915.1		n.370G>A		non_coding_transcript_exon	Exon 3 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CUZD1	ENST00000338948.3	TSL:1	n.-307G>A	non_coding_transcript_exon	Exon 1 of 4	ENSP00000340905.4	A0A0A0MRA6
CUZD1	ENST00000368900.5	TSL:1	n.-307G>A	non_coding_transcript_exon	Exon 1 of 8	ENSP00000357896.2	A0A0A0MRL2
CUZD1	ENST00000368901.5	TSL:1	n.-307G>A	non_coding_transcript_exon	Exon 1 of 8	ENSP00000357897.2	A0A0A0MRL2

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over