rs11248321

Positions:

• chr10-122834637-A-G
• chr10-122834637-A-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUZD1	NM_022034.6	c.1382+69T>C		intron_variant		ENST00000392790.6
FAM24B-CUZD1	NR_037915.1	n.2058+69T>C		intron_variant, non_coding_transcript_variant
CUZD1	NR_037912.2	n.1245+69T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUZD1	ENST00000392790.6	c.1382+69T>C		intron_variant		1	NM_022034.6	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70817 AN: 151812 Hom.: 17819 Cov.: 32

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

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.537

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.479

Gnomad4 FIN exome AF: 0.613

Gnomad4 NFE exome AF: 0.546

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.466 AC: 70828 AN: 151928 Hom.: 17816 Cov.: 32 AF XY: 0.469 AC XY: 34852 AN XY: 74250

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.485

Alfa AF: 0.523 Hom.: 7662

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
DANN	Benign	0.79

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: rs11248321; hg19: chr10-124594153; COSMIC: COSV59026627;