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
• Publications: 5 publications found

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]

CDC73 Gene-Disease associations (from GenCC):

• hyperparathyroidism 2 with jaw tumors

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
• hyperparathyroidism 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• parathyroid gland carcinoma

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial isolated hyperparathyroidism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024529.5. 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
	CDC73	NM_024529.5	MANE Select	c.1418-17C>G		intron	N/A	NP_078805.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC73	ENST00000367435.5	TSL:1 MANE Select	c.1418-17C>G		intron	N/A	ENSP00000356405.4
	CDC73	ENST00000958309.1		c.1418-17C>G		intron	N/A	ENSP00000628368.1
	CDC73	ENST00000958310.1		c.1415-17C>G		intron	N/A	ENSP00000628369.1

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

African (AFR) AF: 0.0127 AC: 420 AN: 33106

American (AMR) AF: 0.0397 AC: 1770 AN: 44558

Ashkenazi Jewish (ASJ) AF: 0.0792 AC: 2056 AN: 25950

East Asian (EAS) AF: 0.000203 AC: 8 AN: 39500

South Asian (SAS) AF: 0.0211 AC: 1810 AN: 85822

European-Finnish (FIN) AF: 0.0609 AC: 3243 AN: 53286

Middle Eastern (MID) AF: 0.0406 AC: 232 AN: 5720

European-Non Finnish (NFE) AF: 0.0914 AC: 99949 AN: 1093196

Other (OTH) 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

African (AFR) AF: 0.0170 AC: 705 AN: 41468

American (AMR) AF: 0.0516 AC: 785 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.0771 AC: 267 AN: 3462

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5168

South Asian (SAS) AF: 0.0200 AC: 96 AN: 4804

European-Finnish (FIN) AF: 0.0634 AC: 668 AN: 10532

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0901 AC: 6107 AN: 67800

Other (OTH) AF: 0.0704 AC: 148 AN: 2102

Alfa AF: 0.0481 Hom.: 59

Bravo AF: 0.0572

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hyperparathyroidism 2 with jaw tumors (1)
-	-	1	not specified (1)
-	-	1	Parathyroid carcinoma (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.97
DANN	Benign	0.39
PhyloP100		-0.17
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

Other links and lift over

dbSNP: rs11583414; hg19: chr1-193218843;