rs2077464

Positions:

• chr17-40290312-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001254.4(CDC6):​c.178+714A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,014 control chromosomes in the GnomAD database, including 6,268 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 0.24 (6268 hom., cov: 32)
• Consequence: CDC6 NM_001254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

Genes affected

CDC6 (HGNC:1744): (cell division cycle 6) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc6, a protein essential for the initiation of DNA replication. This protein functions as a regulator at the early steps of DNA replication. It localizes in cell nucleus during cell cyle G1, but translocates to the cytoplasm at the start of S phase. The subcellular translocation of this protein during cell cyle is regulated through its phosphorylation by Cdks. Transcription of this protein was reported to be regulated in response to mitogenic signals through transcriptional control mechanism involving E2F proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC6	NM_001254.4	c.178+714A>G		intron_variant		ENST00000209728.9	NP_001245.1
CDC6	XM_011525541.3	c.178+714A>G		intron_variant			XP_011523843.1
CDC6	XM_011525542.2	c.178+714A>G		intron_variant			XP_011523844.1
CDC6	XM_047437207.1	c.178+714A>G		intron_variant			XP_047293163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC6	ENST00000209728.9	c.178+714A>G		intron_variant		1	NM_001254.4	ENSP00000209728	P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36326 AN: 151896 Hom.: 6228 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.240 AC: 36427 AN: 152014 Hom.: 6268 Cov.: 32 AF XY: 0.239 AC XY: 17725 AN XY: 74282

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.194

Alfa AF: 0.152 Hom.: 2117

Bravo AF: 0.255

Asia WGS AF: 0.239 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.3
DANN	Benign	0.76

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: rs2077464; hg19: chr17-38446564;