1-91500888-A-G

Position:

• chr1-91500888-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003503.4(CDC7):​c.-124A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,154 control chromosomes in the GnomAD database, including 6,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6518 hom., cov: 33)
  • Exomes 𝑓: 0.45 (9 hom.)
• Consequence: CDC7 NM_003503.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.04

Genes affected

CDC7 (HGNC:1745): (cell division cycle 7) This gene encodes a cell division cycle protein with kinase activity that is critical for the G1/S transition. The yeast homolog is also essential for initiation of DNA replication as cell division occurs. Overexpression of this gene product may be associated with neoplastic transformation for some tumors. Multiple alternatively spliced transcript variants that encode the same protein have been detected. [provided by RefSeq, Aug 2008]

LOC105378856 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-91500888-A-G is Benign according to our data. Variant chr1-91500888-A-G is described in ClinVar as [Benign]. Clinvar id is 1272528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-91500888-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC7	NM_003503.4	c.-124A>G		5_prime_UTR_variant	1/12	ENST00000234626.11	NP_003494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC7	ENST00000234626	c.-124A>G		5_prime_UTR_variant	1/12	1	NM_003503.4	ENSP00000234626.6

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39895 AN: 151962 Hom.: 6518 Cov.: 33

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.0668

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.446 AC: 33 AN: 74 Hom.: 9 Cov.: 0 AF XY: 0.468 AC XY: 29 AN XY: 62

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.262 AC: 39912 AN: 152080 Hom.: 6518 Cov.: 33 AF XY: 0.259 AC XY: 19246 AN XY: 74354

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.0672

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.275

Alfa AF: 0.339 Hom.: 10105

Bravo AF: 0.250

Asia WGS AF: 0.126 AC: 441 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2019	This variant is associated with the following publications: (PMID: 30823486) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.2
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13447455; hg19: chr1-91966445; COSMIC: COSV52309877;