chr1-183647970-A-G

Variant names:

• chr1-183647970-A-G
• rs1174658
• NM_203454.3:c.812T>C

Variant summary

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

The NM_203454.3(APOBEC4):​c.812T>C​(p.Phe271Ser) 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 1,613,898 control chromosomes in the GnomAD database, including 126,235 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 (12212 hom., cov: 32)
  • Exomes 𝑓: 0.39 (114023 hom.)
• Consequence: APOBEC4 NM_203454.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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=2.2375584E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC4	NM_203454.3	c.812T>C	p.Phe271Ser	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.812T>C	p.Phe271Ser	missense_variant	Exon 2 of 2	1	NM_203454.3	ENSP00000310622.4
RGL1	ENST00000304685.8	c.-33+11469A>G		intron_variant	Intron 1 of 18	1		ENSP00000303192.3
APOBEC4	ENST00000481562.1	n.246-173T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60336 AN: 151926 Hom.: 12193 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.338

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: 91333 AN: 251408 Hom.: 17096 AF XY: 0.362 AC XY: 49237 AN XY: 135880

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: 572193 AN: 1461854 Hom.: 114023 Cov.: 65 AF XY: 0.389 AC XY: 282871 AN XY: 727228

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.367

Gnomad4 EAS exome AF: 0.185

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: 60395 AN: 152044 Hom.: 12212 Cov.: 32 AF XY: 0.392 AC XY: 29136 AN XY: 74300

Gnomad4 AFR AF: 0.471

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.: 24871

Bravo AF: 0.400

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: 44661

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	0.044
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.4
DANN	Benign	0.53
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00032	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.00022	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.2	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	3.1	N
REVEL	Benign	0.087
Sift	Benign	0.76	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.024
MPC		0.19
ClinPred		0.0059	T
GERP RS		4.5
Varity_R		0.054
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs1174658; hg19: chr1-183617105; COSMIC: COSV58017675;