chr1-183647791-T-C

Variant names:

• chr1-183647791-T-C
• rs1174657
• NM_203454.3:c.991A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203454.3(APOBEC4):​c.991A>G​(p.Lys331Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,613,798 control chromosomes in the GnomAD database, including 126,232 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.40 (12181 hom., cov: 32)
  • Exomes 𝑓: 0.39 (114051 hom.)
• Consequence: APOBEC4 NM_203454.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.220571E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC4	NM_203454.3	c.991A>G	p.Lys331Glu	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.991A>G	p.Lys331Glu	missense_variant	Exon 2 of 2	1	NM_203454.3	ENSP00000310622.4
RGL1	ENST00000304685.8	c.-33+11290T>C		intron_variant	Intron 1 of 18	1		ENSP00000303192.3
APOBEC4	ENST00000481562.1	n.252A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60265 AN: 151846 Hom.: 12162 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.379

GnomAD3 exomes AF: 0.363 AC: 91341 AN: 251460 Hom.: 17103 AF XY: 0.362 AC XY: 49242 AN XY: 135906

Gnomad AFR exome AF: 0.475

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.230

Gnomad SAS exome AF: 0.327

Gnomad FIN exome AF: 0.359

Gnomad NFE exome AF: 0.397

Gnomad OTH exome AF: 0.377

GnomAD4 exome AF: 0.391 AC: 572250 AN: 1461834 Hom.: 114051 Cov.: 58 AF XY: 0.389 AC XY: 282902 AN XY: 727224

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.367

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.397 AC: 60324 AN: 151964 Hom.: 12181 Cov.: 32 AF XY: 0.392 AC XY: 29108 AN XY: 74278

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.376

Alfa AF: 0.390 Hom.: 27917

Bravo AF: 0.401

TwinsUK AF: 0.408 AC: 1514

ALSPAC AF: 0.426 AC: 1643

ESP6500AA AF: 0.469 AC: 2068

ESP6500EA AF: 0.395 AC: 3401

ExAC AF: 0.368 AC: 44672

Asia WGS AF: 0.274 AC: 955 AN: 3478

EpiCase AF: 0.397

EpiControl AF: 0.392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.31
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.00022	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.046
Sift	Benign	0.74	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.021
MPC		0.15
ClinPred		0.0053	T
GERP RS		-0.47
Varity_R		0.073
gMVP		0.087

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1174657; hg19: chr1-183616926; COSMIC: COSV58017117;