1-193245593-A-G

Position:

• chr1-193245593-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.1418-4137A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 152,222 control chromosomes in the GnomAD database, including 490 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 0.048 (490 hom., cov: 32)
• Consequence: CDC73 NM_024529.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC73	NM_024529.5	c.1418-4137A>G		intron_variant		ENST00000367435.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC73	ENST00000367435.5	c.1418-4137A>G		intron_variant		1	NM_024529.5	P1

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7270 AN: 152104 Hom.: 489 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.00876

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00563

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0478 AC: 7274 AN: 152222 Hom.: 490 Cov.: 32 AF XY: 0.0465 AC XY: 3463 AN XY: 74428

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.0268

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.00876

Gnomad4 NFE AF: 0.00563

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0323 Hom.: 44

Bravo AF: 0.0533

Asia WGS AF: 0.0360 AC: 124 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.47

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: rs7525286; hg19: chr1-193214723;