1-193228277-A-G

Variant names:

• chr1-193228277-A-G
• rs1408830
• NM_024529.5:c.1155-4716A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024529.5(CDC73):​c.1155-4716A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,932 control chromosomes in the GnomAD database, including 30,035 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 0.62 (30035 hom., cov: 31)
• Consequence: CDC73 NM_024529.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• 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), Ambry Genetics, G2P, ClinGen
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.748 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.1155-4716A>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.1155-4716A>G		intron	N/A	ENSP00000356405.4	Q6P1J9
	CDC73	ENST00000958309.1		c.1155-4716A>G		intron	N/A	ENSP00000628368.1
	CDC73	ENST00000958310.1		c.1152-4716A>G		intron	N/A	ENSP00000628369.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94746 AN: 151814 Hom.: 30012 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.624 AC: 94809 AN: 151932 Hom.: 30035 Cov.: 31 AF XY: 0.626 AC XY: 46467 AN XY: 74252

African (AFR) AF: 0.521 AC: 21591 AN: 41412

American (AMR) AF: 0.673 AC: 10269 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2338 AN: 3472

East Asian (EAS) AF: 0.450 AC: 2331 AN: 5176

South Asian (SAS) AF: 0.769 AC: 3702 AN: 4816

European-Finnish (FIN) AF: 0.619 AC: 6520 AN: 10534

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45810 AN: 67962

Other (OTH) AF: 0.654 AC: 1374 AN: 2102

Alfa AF: 0.599 Hom.: 6793

Bravo AF: 0.617

Asia WGS AF: 0.643 AC: 2232 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.71
PhyloP100		-0.30
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: rs1408830; hg19: chr1-193197407;