9-34107234-T-C

Position:

• chr9-34107234-T-C

Variant summary

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

The NM_015397.4(DCAF12):​c.540+125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 908,578 control chromosomes in the GnomAD database, including 242,237 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 0.70 (38052 hom., cov: 31)
  • Exomes 𝑓: 0.73 (204185 hom.)
• Consequence: DCAF12 NM_015397.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333

Genes affected

DCAF12 (HGNC:19911): (DDB1 and CUL4 associated factor 12) This gene encodes a WD repeat-containing protein that interacts with the COP9 signalosome, a macromolecular complex that interacts with cullin-RING E3 ligases and regulates their activity by hydrolyzing cullin-Nedd8 conjugates. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF12	NM_015397.4	c.540+125A>G		intron_variant		ENST00000361264.9	NP_056212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF12	ENST00000361264.9	c.540+125A>G		intron_variant		1	NM_015397.4	ENSP00000355114	P1
DCAF12	ENST00000396990.6	c.486+125A>G		intron_variant		3		ENSP00000380187
DCAF12	ENST00000450964.1	c.477+125A>G		intron_variant		5		ENSP00000415833

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106434 AN: 151872 Hom.: 38020 Cov.: 31

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.713

GnomAD4 exome AF: 0.726 AC: 549458 AN: 756588 Hom.: 204185 AF XY: 0.726 AC XY: 286444 AN XY: 394742

Gnomad4 AFR exome AF: 0.628

Gnomad4 AMR exome AF: 0.651

Gnomad4 ASJ exome AF: 0.755

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.680

Gnomad4 FIN exome AF: 0.756

Gnomad4 NFE exome AF: 0.769

Gnomad4 OTH exome AF: 0.719

GnomAD4 genome AF: 0.701 AC: 106514 AN: 151990 Hom.: 38052 Cov.: 31 AF XY: 0.697 AC XY: 51748 AN XY: 74282

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.714

Alfa AF: 0.733 Hom.: 14215

Bravo AF: 0.686

Asia WGS AF: 0.540 AC: 1875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.61

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: rs10511914; hg19: chr9-34107232; COSMIC: COSV63514319; COSMIC: COSV63514319;