9-34107234-T-C

Variant names:

• chr9-34107234-T-C
• rs10511914
• NM_015397.4:c.540+125A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ENSG00000228352 (HGNC:58097):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DCAF12	NM_015397.4	c.540+125A>G		intron_variant	Intron 3 of 8	ENST00000361264.9	NP_056212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF12	ENST00000361264.9	c.540+125A>G		intron_variant	Intron 3 of 8	1	NM_015397.4	ENSP00000355114.3

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

African (AFR) AF: 0.628 AC: 12487 AN: 19882

American (AMR) AF: 0.651 AC: 22641 AN: 34756

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 14248 AN: 18860

East Asian (EAS) AF: 0.285 AC: 10067 AN: 35334

South Asian (SAS) AF: 0.680 AC: 43129 AN: 63412

European-Finnish (FIN) AF: 0.756 AC: 35251 AN: 46654

Middle Eastern (MID) AF: 0.704 AC: 1882 AN: 2674

European-Non Finnish (NFE) AF: 0.769 AC: 383275 AN: 498210

Other (OTH) AF: 0.719 AC: 26478 AN: 36806

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

African (AFR) AF: 0.633 AC: 26241 AN: 41456

American (AMR) AF: 0.669 AC: 10199 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2623 AN: 3470

East Asian (EAS) AF: 0.328 AC: 1695 AN: 5164

South Asian (SAS) AF: 0.682 AC: 3283 AN: 4812

European-Finnish (FIN) AF: 0.746 AC: 7877 AN: 10562

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52231 AN: 67964

Other (OTH) AF: 0.714 AC: 1507 AN: 2110

Alfa AF: 0.731 Hom.: 17458

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
PhyloP100		-0.33
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: rs10511914; hg19: chr9-34107232; COSMIC: COSV63514319; COSMIC: COSV63514319;