chr1-183647791-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 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 0.40 (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
• Publications: 40 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=2.220571E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

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.991A>G	p.Lys331Glu	missense	Exon 2 of 2	NP_982279.1
	RGL1	NM_015149.6		c.-33+11290T>C		intron	N/A	NP_055964.3
	RGL1	NM_001297669.3		c.-143+11290T>C		intron	N/A	NP_001284598.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC4	ENST00000308641.6	TSL:1 MANE Select	c.991A>G	p.Lys331Glu	missense	Exon 2 of 2	ENSP00000310622.4
	RGL1	ENST00000304685.8	TSL:1	c.-33+11290T>C		intron	N/A	ENSP00000303192.3
	APOBEC4	ENST00000481562.1	TSL:3	n.252A>G		non_coding_transcript_exon	Exon 2 of 2

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

GnomAD2 exomes AF: 0.363 AC: 91341 AN: 251460 AF XY: 0.362

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 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

African (AFR) AF: 0.481 AC: 16103 AN: 33478

American (AMR) AF: 0.304 AC: 13601 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 9586 AN: 26136

East Asian (EAS) AF: 0.186 AC: 7367 AN: 39700

South Asian (SAS) AF: 0.329 AC: 28351 AN: 86252

European-Finnish (FIN) AF: 0.362 AC: 19341 AN: 53414

Middle Eastern (MID) AF: 0.450 AC: 2592 AN: 5766

European-Non Finnish (NFE) AF: 0.406 AC: 451572 AN: 1111978

Other (OTH) AF: 0.393 AC: 23737 AN: 60388

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

African (AFR) AF: 0.470 AC: 19458 AN: 41420

American (AMR) AF: 0.337 AC: 5143 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1245 AN: 3472

East Asian (EAS) AF: 0.213 AC: 1104 AN: 5180

South Asian (SAS) AF: 0.315 AC: 1518 AN: 4818

European-Finnish (FIN) AF: 0.362 AC: 3824 AN: 10552

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26870 AN: 67930

Other (OTH) AF: 0.376 AC: 795 AN: 2112

Alfa AF: 0.393 Hom.: 42729

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 v4.9

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
PhyloP100		0.037
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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