chr1-183648058-C-T

Variant names:

• chr1-183648058-C-T
• NM_203454.3:c.724G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203454.3(APOBEC4):​c.724G>A​(p.Val242Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOBEC4 NM_203454.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

Genes affected

APOBEC4 (HGNC:32152): (apolipoprotein B mRNA editing enzyme catalytic polypeptide like 4) This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection. [provided by RefSeq, Jul 2008]

RGL1 (HGNC:30281): (ral guanine nucleotide dissociation stimulator like 1) Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05530736).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203454.3. 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
	APOBEC4	NM_203454.3	MANE Select	c.724G>A	p.Val242Ile	missense	Exon 2 of 2	NP_982279.1	Q8WW27
	RGL1	NM_015149.6		c.-33+11557C>T		intron	N/A	NP_055964.3
	RGL1	NM_001297669.3		c.-143+11557C>T		intron	N/A	NP_001284598.1	B7Z2W5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC4	ENST00000308641.6	TSL:1 MANE Select	c.724G>A	p.Val242Ile	missense	Exon 2 of 2	ENSP00000310622.4	Q8WW27
	RGL1	ENST00000304685.8	TSL:1	c.-33+11557C>T		intron	N/A	ENSP00000303192.3	Q9NZL6-2
	APOBEC4	ENST00000481562.1	TSL:3	n.246-261G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Benign	0.092
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.4
DANN	Benign	0.63
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.1
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.030
Sift	Benign	0.43	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.077
MutPred		0.20		Loss of ubiquitination at K247 (P = 0.0747)
MVP		0.048
MPC		0.087
ClinPred		0.064	T
GERP RS		2.3
Varity_R		0.041
gMVP		0.17
Mutation Taster		=99/1	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

hg19: chr1-183617193;