rs80356646

Positions:

• chr1-193142098-TGAGAGAGA-T
• chr1-193142098-TGAGAGAGA-TGA
• chr1-193142098-TGAGAGAGA-TGAGA
• chr1-193142098-TGAGAGAGA-TGAGAGA
• chr1-193142098-TGAGAGAGA-TGAGAGAGAGA
• chr1-193142098-TGAGAGAGA-TGAGAGAGAGAGA
• chr1-193142098-TGAGAGAGA-TGAGAGAGAGAGAGA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000367435.5(CDC73):​c.729+44_729+51del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,437,930 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: CDC73 ENST00000367435.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000202 (3/148738) while in subpopulation AFR AF= 0.0000739 (3/40588). AF 95% confidence interval is 0.0000196. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC73	NM_024529.5	c.729+44_729+51del		intron_variant		ENST00000367435.5	NP_078805.3
CDC73	XM_006711537.5	c.729+44_729+51del		intron_variant			XP_006711600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC73	ENST00000367435.5	c.729+44_729+51del		intron_variant		1	NM_024529.5	ENSP00000356405	P1

Frequencies

GnomAD3 genomes AF: 0.0000202 AC: 3 AN: 148738 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000739

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000931 AC: 12 AN: 1289192 Hom.: 0 AF XY: 0.00000617 AC XY: 4 AN XY: 648194

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000208

Gnomad4 OTH exome AF: 0.0000368

GnomAD4 genome AF: 0.0000202 AC: 3 AN: 148738 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72446

Gnomad4 AFR AF: 0.0000739

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs80356646; hg19: chr1-193111228;