13-113209730-G-C

Variant names:

• chr13-113209730-G-C
• rs1163049031
• NM_001008895.4:c.103G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001008895.4(CUL4A):​c.103G>C​(p.Gly35Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,165,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: CUL4A NM_001008895.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.77
• Publications: 0 publications found

Genes affected

CUL4A (HGNC:2554): (cullin 4A) CUL4A is the ubiquitin ligase component of a multimeric complex involved in the degradation of DNA damage-response proteins (Liu et al., 2009 [PubMed 19481525]).[supplied by OMIM, Oct 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26867783).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008895.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4A	NM_001008895.4	MANE Select	c.103G>C	p.Gly35Arg	missense	Exon 1 of 20	NP_001008895.1	Q13619-1
	CUL4A	NM_001354943.2		c.103G>C	p.Gly35Arg	missense	Exon 1 of 6	NP_001341872.1	A0A087WWN2
	CUL4A	NM_001354940.2		c.-173G>C		5_prime_UTR	Exon 1 of 20	NP_001341869.1	Q13619-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4A	ENST00000375440.9	TSL:1 MANE Select	c.103G>C	p.Gly35Arg	missense	Exon 1 of 20	ENSP00000364589.4	Q13619-1
	CUL4A	ENST00000326335.8	TSL:1	c.-152-243G>C		intron	N/A	ENSP00000322132.5	A0A0A0MR50
	CUL4A	ENST00000375441.7	TSL:1	c.-152-243G>C		intron	N/A	ENSP00000364590.3	Q13619-2

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 4 AN: 149362 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000802

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000984 AC: 10 AN: 1016484 Hom.: 0 Cov.: 30 AF XY: 0.00000626 AC XY: 3 AN XY: 479360

African (AFR) AF: 0.00 AC: 0 AN: 20668

American (AMR) AF: 0.00 AC: 0 AN: 6272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11280

East Asian (EAS) AF: 0.000379 AC: 8 AN: 21118

South Asian (SAS) AF: 0.0000523 AC: 1 AN: 19124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2588

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 878850

Other (OTH) AF: 0.0000258 AC: 1 AN: 38718

GnomAD4 genome AF: 0.0000268 AC: 4 AN: 149362 Hom.: 0 Cov.: 30 AF XY: 0.0000137 AC XY: 1 AN XY: 72864

African (AFR) AF: 0.00 AC: 0 AN: 41084

American (AMR) AF: 0.00 AC: 0 AN: 15080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.000802 AC: 4 AN: 4990

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67022

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000604

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.8
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.14
Sift	Benign	0.077	T
Sift4G	Benign	0.23	T
Polyphen		0.83	P
Vest4		0.26
MutPred		0.36		Gain of catalytic residue at K33 (P = 2e-04)
MVP		0.84
MPC		0.54
ClinPred		0.38	T
GERP RS		3.6
PromoterAI		0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.052
gMVP		0.25
Mutation Taster		=90/10	polymorphism

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: rs1163049031; hg19: chr13-113864044;