rs11583414

Variant names:

• chr1-193249713-C-G
• rs11583414
• NM_024529.5:c.1418-17C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-193249713-C-G
• chr1-193249713-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024529.5(CDC73):​c.1418-17C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0769 in 1,592,552 control chromosomes in the GnomAD database, including 5,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (364 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5024 hom.)
• Consequence: CDC73 NM_024529.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6 O:1
• Conservation: PhyloP100: -0.170

Genes affected

CDC73 (HGNC:16783): (cell division cycle 73) This gene encodes a tumor suppressor that is involved in transcriptional and post-transcriptional control pathways. The protein is a component of the the PAF protein complex, which associates with the RNA polymerase II subunit POLR2A and with a histone methyltransferase complex. This protein appears to facilitate the association of 3' mRNA processing factors with actively-transcribed chromatin. Mutations in this gene have been linked to hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism, and parathyroid carcinoma. [provided by RefSeq, Jul 2009]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-193249713-C-G is Benign according to our data. Variant chr1-193249713-C-G is described in ClinVar as [Benign]. Clinvar id is 21682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC73	NM_024529.5	c.1418-17C>G		intron_variant	Intron 15 of 16	ENST00000367435.5	NP_078805.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC73	ENST00000367435.5	c.1418-17C>G		intron_variant	Intron 15 of 16	1	NM_024529.5	ENSP00000356405.4

Frequencies

GnomAD3 genomes AF: 0.0589 AC: 8936 AN: 151634 Hom.: 364 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.0771

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0200

Gnomad FIN AF: 0.0634

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0900

Gnomad OTH AF: 0.0716

GnomAD2 exomes AF: 0.0592 AC: 14789 AN: 249960 AF XY: 0.0596

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.0386

Gnomad ASJ exome AF: 0.0779

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0600

Gnomad NFE exome AF: 0.0901

Gnomad OTH exome AF: 0.0648

GnomAD4 exome AF: 0.0788 AC: 113566 AN: 1440802 Hom.: 5024 Cov.: 28 AF XY: 0.0776 AC XY: 55688 AN XY: 718040

Gnomad4 AFR exome AF: 0.0127 AC: 420 AN: 33106

Gnomad4 AMR exome AF: 0.0397 AC: 1770 AN: 44558

Gnomad4 ASJ exome AF: 0.0792 AC: 2056 AN: 25950

Gnomad4 EAS exome AF: 0.000203 AC: 8 AN: 39500

Gnomad4 SAS exome AF: 0.0211 AC: 1810 AN: 85822

Gnomad4 FIN exome AF: 0.0609 AC: 3243 AN: 53286

Gnomad4 NFE exome AF: 0.0914 AC: 99949 AN: 1093196

Gnomad4 Remaining exome AF: 0.0683 AC: 4078 AN: 59664

GnomAD4 genome AF: 0.0589 AC: 8936 AN: 151750 Hom.: 364 Cov.: 32 AF XY: 0.0568 AC XY: 4216 AN XY: 74178

Gnomad4 AFR AF: 0.0170 AC: 0.0170011 AN: 0.0170011

Gnomad4 AMR AF: 0.0516 AC: 0.0516176 AN: 0.0516176

Gnomad4 ASJ AF: 0.0771 AC: 0.0771231 AN: 0.0771231

Gnomad4 EAS AF: 0.000580 AC: 0.000580495 AN: 0.000580495

Gnomad4 SAS AF: 0.0200 AC: 0.0199833 AN: 0.0199833

Gnomad4 FIN AF: 0.0634 AC: 0.0634258 AN: 0.0634258

Gnomad4 NFE AF: 0.0901 AC: 0.0900737 AN: 0.0900737

Gnomad4 OTH AF: 0.0704 AC: 0.0704091 AN: 0.0704091

Alfa AF: 0.0481 Hom.: 59

Bravo AF: 0.0572

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Apr 28, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: c.1418-17C>G in the CDC73 gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 5.97%, including numerous homozygous occurrences. The observed frequency greatly exceeds the maximum expected allele frequency for a pathogenic variant of 0.0004%, suggesting that it is a benign polymorphism. The variant of interest has been reported as Benign/Polymorphism by a reputable database and published reports (Newey, 2010; Frank-Raue, 2011). Taking together, based on the prevalence of this variant in general population the variant was classified as Benign. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Parathyroid carcinoma Benign:1 Other:1

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GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hyperparathyroidism 2 with jaw tumors Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.97
DANN	Benign	0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs11583414; hg19: chr1-193218843;