10-122841998-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022034.6(CUZD1):c.83-670A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,678 control chromosomes in the GnomAD database, including 14,997 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 0.44 (14997 hom., cov: 31)
• Consequence: CUZD1 NM_022034.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

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]

FAM24B-CUZD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUZD1	NM_022034.6	c.83-670A>G		intron_variant		ENST00000392790.6
FAM24B-CUZD1	NR_037915.1	n.759-670A>G		intron_variant, non_coding_transcript_variant
CUZD1	NR_037912.2	n.97-2767A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUZD1	ENST00000392790.6	c.83-670A>G		intron_variant		1	NM_022034.6	P1
CUZD1	ENST00000338948.3	c.82+3764A>G		intron_variant, NMD_transcript_variant		1
CUZD1	ENST00000368900.5	c.83-2767A>G		intron_variant, NMD_transcript_variant		1
CUZD1	ENST00000368901.5	c.83-2767A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67109 AN: 151560 Hom.: 14990 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.455

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.443 AC: 67142 AN: 151678 Hom.: 14997 Cov.: 31 AF XY: 0.441 AC XY: 32708 AN XY: 74100

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.457

Alfa AF: 0.449 Hom.: 1946

Bravo AF: 0.453

Asia WGS AF: 0.504 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	14
Dann	Benign	0.94

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

LitVar

Other links and lift over

dbSNP: rs2950366; hg19: chr10-124601514;