rs6977687

Variant names:

• chr7-87908712-G-A
• rs6977687
• NM_006716.4:c.*549G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006716.4(DBF4):​c.*549G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,016 control chromosomes in the GnomAD database, including 7,440 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 (7440 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: DBF4 NM_006716.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 8 publications found

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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBF4	NM_006716.4	c.*549G>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000265728.6	NP_006707.1
DBF4	NM_001318061.2	c.*549G>A		3_prime_UTR_variant	Exon 12 of 12		NP_001304990.1
DBF4	NM_001318060.2	c.*549G>A		3_prime_UTR_variant	Exon 11 of 11		NP_001304989.1
DBF4	NM_001318062.2	c.*549G>A		3_prime_UTR_variant	Exon 12 of 12		NP_001304991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBF4	ENST00000265728.6	c.*549G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_006716.4	ENSP00000265728.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42796 AN: 151886 Hom.: 7410 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.0833 AC: 1 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.282 AC: 42886 AN: 152004 Hom.: 7440 Cov.: 32 AF XY: 0.282 AC XY: 20947 AN XY: 74314

African (AFR) AF: 0.478 AC: 19811 AN: 41414

American (AMR) AF: 0.337 AC: 5142 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3470

East Asian (EAS) AF: 0.293 AC: 1513 AN: 5164

South Asian (SAS) AF: 0.195 AC: 942 AN: 4830

European-Finnish (FIN) AF: 0.146 AC: 1550 AN: 10584

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12293 AN: 67966

Other (OTH) AF: 0.289 AC: 608 AN: 2104

Alfa AF: 0.216 Hom.: 4533

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	-0.86
CADD	Benign	0.88
DANN	Benign	0.74
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6977687; hg19: chr7-87538027;