1-183647749-C-T

Variant names:

• chr1-183647749-C-T
• rs10911390
• NM_203454.3:c.1033G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203454.3(APOBEC4):​c.1033G>A​(p.Val345Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,613,802 control chromosomes in the GnomAD database, including 2,030 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.069 (626 hom., cov: 33)
  • Exomes 𝑓: 0.035 (1404 hom.)
• Consequence: APOBEC4 NM_203454.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238
• Publications: 29 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025907457).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC4	NM_203454.3	c.1033G>A	p.Val345Met	missense_variant	Exon 2 of 2	ENST00000308641.6	NP_982279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC4	ENST00000308641.6	c.1033G>A	p.Val345Met	missense_variant	Exon 2 of 2	1	NM_203454.3	ENSP00000310622.4
RGL1	ENST00000304685.8	c.-33+11248C>T		intron_variant	Intron 1 of 18	1		ENSP00000303192.3
APOBEC4	ENST00000481562.1	n.294G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10417 AN: 152108 Hom.: 620 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.0803

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0287

Gnomad OTH AF: 0.0602

GnomAD2 exomes AF: 0.0434 AC: 10896 AN: 251340 AF XY: 0.0429

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.0168

Gnomad ASJ exome AF: 0.0123

Gnomad EAS exome AF: 0.0830

Gnomad FIN exome AF: 0.0272

Gnomad NFE exome AF: 0.0279

Gnomad OTH exome AF: 0.0356

GnomAD4 exome AF: 0.0348 AC: 50922 AN: 1461576 Hom.: 1404 Cov.: 30 AF XY: 0.0354 AC XY: 25703 AN XY: 727084

African (AFR) AF: 0.171 AC: 5719 AN: 33458

American (AMR) AF: 0.0182 AC: 814 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 353 AN: 26124

East Asian (EAS) AF: 0.0450 AC: 1788 AN: 39690

South Asian (SAS) AF: 0.0661 AC: 5696 AN: 86234

European-Finnish (FIN) AF: 0.0265 AC: 1416 AN: 53416

Middle Eastern (MID) AF: 0.0480 AC: 277 AN: 5768

European-Non Finnish (NFE) AF: 0.0291 AC: 32332 AN: 1111796

Other (OTH) AF: 0.0419 AC: 2527 AN: 60380

GnomAD4 genome AF: 0.0686 AC: 10438 AN: 152226 Hom.: 626 Cov.: 33 AF XY: 0.0675 AC XY: 5022 AN XY: 74436

African (AFR) AF: 0.163 AC: 6760 AN: 41508

American (AMR) AF: 0.0347 AC: 531 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3470

East Asian (EAS) AF: 0.0809 AC: 419 AN: 5178

South Asian (SAS) AF: 0.0629 AC: 304 AN: 4830

European-Finnish (FIN) AF: 0.0262 AC: 278 AN: 10606

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0287 AC: 1954 AN: 68008

Other (OTH) AF: 0.0591 AC: 125 AN: 2116

Alfa AF: 0.0389 Hom.: 752

Bravo AF: 0.0732

TwinsUK AF: 0.0264 AC: 98

ALSPAC AF: 0.0278 AC: 107

ESP6500AA AF: 0.152 AC: 668

ESP6500EA AF: 0.0281 AC: 242

ExAC AF: 0.0460 AC: 5588

Asia WGS AF: 0.0720 AC: 252 AN: 3478

EpiCase AF: 0.0303

EpiControl AF: 0.0286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.9
DANN	Benign	0.86
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.24
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.14
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.032	D
Polyphen		0.088	B
Vest4		0.047
MPC		0.12
ClinPred		0.0027	T
GERP RS		3.3
Varity_R		0.11
gMVP		0.13
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs10911390; hg19: chr1-183616884; COSMIC: COSV58017112;