1-193228277-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC73	NM_024529.5	c.1155-4716A>G		intron_variant		ENST00000367435.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC73	ENST00000367435.5	c.1155-4716A>G		intron_variant		1	NM_024529.5	P1

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

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.654

Alfa AF: 0.544 Hom.: 2110

Bravo AF: 0.617

Asia WGS AF: 0.643 AC: 2232 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.8
Dann	Benign	0.71

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: rs1408830; hg19: chr1-193197407;