1-183647883-T-C

Variant names:

• chr1-183647883-T-C
• rs16861381
• NM_203454.3:c.899A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_203454.3(APOBEC4):​c.899A>G​(p.Asp300Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,614,144 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.013 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (44 hom.)
• Consequence: APOBEC4 NM_203454.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.958

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020916164).
• BP6: Variant 1-183647883-T-C is Benign according to our data. Variant chr1-183647883-T-C is described in ClinVar as [Benign]. Clinvar id is 783957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1916/152254) while in subpopulation AFR AF= 0.0441 (1833/41532). AF 95% confidence interval is 0.0425. There are 46 homozygotes in gnomad4. There are 879 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC4	NM_203454.3	c.899A>G	p.Asp300Gly	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.899A>G	p.Asp300Gly	missense_variant	Exon 2 of 2	1	NM_203454.3	ENSP00000310622.4
RGL1	ENST00000304685.8	c.-33+11382T>C		intron_variant	Intron 1 of 18	1		ENSP00000303192.3
APOBEC4	ENST00000481562.1	n.246-86A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1914 AN: 152136 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00320 AC: 805 AN: 251434 Hom.: 14 AF XY: 0.00248 AC XY: 337 AN XY: 135886

Gnomad AFR exome AF: 0.0455

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.00129 AC: 1890 AN: 1461890 Hom.: 44 Cov.: 66 AF XY: 0.00109 AC XY: 794 AN XY: 727246

Gnomad4 AFR exome AF: 0.0484

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000243

Gnomad4 OTH exome AF: 0.00255

GnomAD4 genome AF: 0.0126 AC: 1916 AN: 152254 Hom.: 46 Cov.: 32 AF XY: 0.0118 AC XY: 879 AN XY: 74452

Gnomad4 AFR AF: 0.0441

Gnomad4 AMR AF: 0.00419

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00246 Hom.: 7

Bravo AF: 0.0149

ESP6500AA AF: 0.0468 AC: 206

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00404 AC: 491

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.83
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.039
Sift	Benign	0.27	T
Sift4G	Benign	0.35	T
Polyphen		0.0010	B
Vest4		0.13
MVP		0.13
MPC		0.14
ClinPred		0.0038	T
GERP RS		2.9
Varity_R		0.075
gMVP		0.20

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: rs16861381; hg19: chr1-183617018;