Variant 1-193125245-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024529.5(CDC73):c.237+28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,232,496 control chromosomes in the GnomAD database, including 271,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30070 hom., cov: 32)

Exomes 𝑓: 0.67 ( 241893 hom. )

Consequence

CDC73
NM_024529.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.05

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-193125245-T-C is Benign according to our data. Variant chr1-193125245-T-C is described in ClinVar as [Benign]. Clinvar id is 1231125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 linkuse as main transcript	c.237+28T>C		intron_variant		ENST00000367435.5
CDC73	XM_006711537.5 linkuse as main transcript	c.237+28T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC73	ENST00000367435.5 linkuse as main transcript	c.237+28T>C		intron_variant		1	NM_024529.5	P1

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94825

AN:

151906

Hom.:

30047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.732

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.673

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.617

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.652

GnomAD3 exomes

AF:

0.652

AC:

162428

AN:

249248

Hom.:

53807

AF XY:

0.661

AC XY:

89101

AN XY:

134860

show subpopulations

Gnomad AFR exome

AF:

0.522

Gnomad AMR exome

AF:

0.637

Gnomad ASJ exome

AF:

0.670

Gnomad EAS exome

AF:

0.449

Gnomad SAS exome

AF:

0.765

Gnomad FIN exome

AF:

0.609

Gnomad NFE exome

AF:

0.682

Gnomad OTH exome

AF:

0.671

GnomAD4 exome

AF:

0.665

AC:

718584

AN:

1080472

Hom.:

241893

Cov.:

AF XY:

0.670

AC XY:

372092

AN XY:

555532

show subpopulations

Gnomad4 AFR exome

AF:

0.518

Gnomad4 AMR exome

AF:

0.637

Gnomad4 ASJ exome

AF:

0.675

Gnomad4 EAS exome

AF:

0.485

Gnomad4 SAS exome

AF:

0.763

Gnomad4 FIN exome

AF:

0.615

Gnomad4 NFE exome

AF:

0.673

Gnomad4 OTH exome

AF:

0.662

GnomAD4 genome

AF:

0.624

AC:

94888

AN:

152024

Hom.:

30070

Cov.:

AF XY:

0.626

AC XY:

46508

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.521

Gnomad4 AMR

AF:

0.674

Gnomad4 ASJ

AF:

0.673

Gnomad4 EAS

AF:

0.452

Gnomad4 SAS

AF:

0.769

Gnomad4 FIN

AF:

0.617

Gnomad4 NFE

AF:

0.674

Gnomad4 OTH

AF:

0.654

Alfa

AF:

0.628

Hom.:

6517

Bravo

AF:

0.617

Asia WGS

AF:

0.643

AC:

2235

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Hyperparathyroidism 2 with jaw tumors

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

6.6

DANN

Benign

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over