rs2275003

Positions:

• chr9-34124862-A-G
• chr9-34124862-A-T

Variant summary

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

The NM_015397.4(DCAF12):​c.333+161T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,996 control chromosomes in the GnomAD database, including 17,263 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 0.47 (17263 hom., cov: 32)
• Consequence: DCAF12 NM_015397.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707

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]

DCAF12 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF12	NM_015397.4	c.333+161T>C		intron_variant		ENST00000361264.9	NP_056212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF12	ENST00000361264.9	c.333+161T>C		intron_variant		1	NM_015397.4	ENSP00000355114.3
DCAF12	ENST00000396990.6	c.279+161T>C		intron_variant		3		ENSP00000380187.2
DCAF12	ENST00000450964.1	c.270+161T>C		intron_variant		5		ENSP00000415833.1
DCAF12	ENST00000463286.1	n.477+161T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71142 AN: 151878 Hom.: 17243 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.468 AC: 71210 AN: 151996 Hom.: 17263 Cov.: 32 AF XY: 0.469 AC XY: 34804 AN XY: 74288

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.471

Alfa AF: 0.504 Hom.: 25856

Bravo AF: 0.450

Asia WGS AF: 0.469 AC: 1631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2275003; hg19: chr9-34124860; COSMIC: COSV63514286;