rs1473447497

Variant names:

• chr7-87900307-A-G
• rs1473447497
• NM_006716.4:c.767A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-87900307-A-G
• chr7-87900307-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006716.4(DBF4):​c.767A>G​(p.Asp256Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,453,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D256V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DBF4 NM_006716.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.00

Genes affected

DBF4 (HGNC:17364): (DBF4-CDC7 kinase regulatory subunit) Predicted to enable protein serine/threonine kinase activator activity. Predicted to be involved in positive regulation of nuclear cell cycle DNA replication and regulation of cell cycle phase transition. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2840798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBF4	NM_006716.4	c.767A>G	p.Asp256Gly	missense_variant	Exon 9 of 12	ENST00000265728.6	NP_006707.1
DBF4	NM_001318061.2	c.95A>G	p.Asp32Gly	missense_variant	Exon 9 of 12		NP_001304990.1
DBF4	NM_001318060.2	c.68A>G	p.Asp23Gly	missense_variant	Exon 8 of 11		NP_001304989.1
DBF4	NM_001318062.2	c.-14A>G		5_prime_UTR_variant	Exon 9 of 12		NP_001304991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBF4	ENST00000265728.6	c.767A>G	p.Asp256Gly	missense_variant	Exon 9 of 12	1	NM_006716.4	ENSP00000265728.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453782 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 722914

African (AFR) AF: 0.00 AC: 0 AN: 32848

American (AMR) AF: 0.00 AC: 0 AN: 42694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25926

East Asian (EAS) AF: 0.00 AC: 0 AN: 39266

South Asian (SAS) AF: 0.00 AC: 0 AN: 84162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109702

Other (OTH) AF: 0.00 AC: 0 AN: 60060

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.0
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.086
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.52	P
Vest4		0.35
MutPred		0.22		Gain of catalytic residue at P252 (P = 0.0678);
MVP		0.24
MPC		0.40
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.56
gMVP		0.31
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

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

Publications

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Other links and lift over

dbSNP: rs1473447497; hg19: chr7-87529622;