rs1223236804

Variant names:

• chr13-113209652-G-A
• rs1223236804
• NM_001008895.4:c.25G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-113209652-G-A
• chr13-113209652-G-C
• chr13-113209652-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008895.4(CUL4A):​c.25G>A​(p.Gly9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000103 in 972,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G9C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: CUL4A NM_001008895.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20532903).

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.25G>A	p.Gly9Ser	missense	Exon 1 of 20	NP_001008895.1	Q13619-1
	CUL4A	NM_001354943.2		c.25G>A	p.Gly9Ser	missense	Exon 1 of 6	NP_001341872.1	A0A087WWN2
	CUL4A	NM_001354940.2		c.-251G>A		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.25G>A	p.Gly9Ser	missense	Exon 1 of 20	ENSP00000364589.4	Q13619-1
	CUL4A	ENST00000326335.8	TSL:1	c.-152-321G>A		intron	N/A	ENSP00000322132.5	A0A0A0MR50
	CUL4A	ENST00000375441.7	TSL:1	c.-152-321G>A		intron	N/A	ENSP00000364590.3	Q13619-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000103 AC: 1 AN: 972154 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 456772

African (AFR) AF: 0.00 AC: 0 AN: 19106

American (AMR) AF: 0.00 AC: 0 AN: 4972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9746

East Asian (EAS) AF: 0.00 AC: 0 AN: 16368

South Asian (SAS) AF: 0.00 AC: 0 AN: 18546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2348

European-Non Finnish (NFE) AF: 0.00000117 AC: 1 AN: 851222

Other (OTH) AF: 0.00 AC: 0 AN: 35906

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.71	N
REVEL	Benign	0.13
Sift	Benign	0.52	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.28		Loss of sheet (P = 0.0181)
MVP		0.61
MPC		0.40
ClinPred		0.27	T
GERP RS		4.0
PromoterAI		0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.054
gMVP		0.24
Mutation Taster		=93/7	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: rs1223236804; hg19: chr13-113863966;