chr1-193236384-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_024529.5(CDC73):​c.1417+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,324,950 control chromosomes in the GnomAD database, including 1 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 0.00035 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

CDC73
NM_024529.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.359
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000348 (53/152222) while in subpopulation EAS AF= 0.00443 (23/5192). AF 95% confidence interval is 0.00303. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 53 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDC73NM_024529.5 linkc.1417+28C>T intron_variant Intron 15 of 16 ENST00000367435.5 NP_078805.3 Q6P1J9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDC73ENST00000367435.5 linkc.1417+28C>T intron_variant Intron 15 of 16 1 NM_024529.5 ENSP00000356405.4 Q6P1J9

Frequencies

GnomAD3 genomes
AF:
0.000348
AC:
53
AN:
152102
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000604
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00442
Gnomad SAS
AF:
0.000830
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000315
AC:
79
AN:
251188
Hom.:
1
AF XY:
0.000280
AC XY:
38
AN XY:
135770
show subpopulations
Gnomad AFR exome
AF:
0.000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00316
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.000109
AC:
128
AN:
1172728
Hom.:
1
Cov.:
16
AF XY:
0.000122
AC XY:
73
AN XY:
597588
show subpopulations
Gnomad4 AFR exome
AF:
0.000322
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00138
Gnomad4 SAS exome
AF:
0.0000746
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000354
Gnomad4 OTH exome
AF:
0.00112
GnomAD4 genome
AF:
0.000348
AC:
53
AN:
152222
Hom.:
0
Cov.:
31
AF XY:
0.000336
AC XY:
25
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.000602
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00443
Gnomad4 SAS
AF:
0.000831
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.000389
Asia WGS
AF:
0.00722
AC:
25
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
5.7
DANN
Benign
0.81
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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.

Other links and lift over

dbSNP: rs368135060; hg19: chr1-193205514; API