7-87905781-T-C

Variant names:

• chr7-87905781-T-C
• rs4728713
• NM_006716.4:c.1049+1365T>C

Variant summary

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

The NM_006716.4(DBF4):​c.1049+1365T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,076 control chromosomes in the GnomAD database, including 7,449 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 0.28 (7449 hom., cov: 32)
• Consequence: DBF4 NM_006716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBF4	NM_006716.4	c.1049+1365T>C		intron_variant	Intron 11 of 11	ENST00000265728.6	NP_006707.1
DBF4	NM_001318061.2	c.377+1365T>C		intron_variant	Intron 11 of 11		NP_001304990.1
DBF4	NM_001318060.2	c.350+1365T>C		intron_variant	Intron 10 of 10		NP_001304989.1
DBF4	NM_001318062.2	c.269+1365T>C		intron_variant	Intron 11 of 11		NP_001304991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBF4	ENST00000265728.6	c.1049+1365T>C		intron_variant	Intron 11 of 11	1	NM_006716.4	ENSP00000265728.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42843 AN: 151958 Hom.: 7419 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.282 AC: 42933 AN: 152076 Hom.: 7449 Cov.: 32 AF XY: 0.282 AC XY: 20988 AN XY: 74340

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.287

Alfa AF: 0.204 Hom.: 1651

Bravo AF: 0.303

Asia WGS AF: 0.258 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.8
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4728713; hg19: chr7-87535096;