1-183648236-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_203454.3(APOBEC4):​c.546G>A​(p.Pro182Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,614,110 control chromosomes in the GnomAD database, including 328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 188 hom., cov: 32)
Exomes 𝑓: 0.0026 ( 140 hom. )

Consequence

APOBEC4
NM_203454.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.23
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 1-183648236-C-T is Benign according to our data. Variant chr1-183648236-C-T is described in ClinVar as [Benign]. Clinvar id is 789700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.23 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0901 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APOBEC4NM_203454.3 linkc.546G>A p.Pro182Pro synonymous_variant Exon 2 of 2 ENST00000308641.6 NP_982279.1 Q8WW27

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APOBEC4ENST00000308641.6 linkc.546G>A p.Pro182Pro synonymous_variant Exon 2 of 2 1 NM_203454.3 ENSP00000310622.4 Q8WW27
RGL1ENST00000304685.8 linkc.-33+11735C>T intron_variant Intron 1 of 18 1 ENSP00000303192.3 Q9NZL6-2
APOBEC4ENST00000481562.1 linkn.246-439G>A intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.0266
AC:
4045
AN:
152130
Hom.:
189
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0927
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.0102
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.0167
GnomAD3 exomes
AF:
0.00672
AC:
1690
AN:
251334
Hom.:
66
AF XY:
0.00492
AC XY:
669
AN XY:
135850
show subpopulations
Gnomad AFR exome
AF:
0.0957
Gnomad AMR exome
AF:
0.00298
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.00179
GnomAD4 exome
AF:
0.00257
AC:
3756
AN:
1461862
Hom.:
140
Cov.:
34
AF XY:
0.00224
AC XY:
1626
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0938
Gnomad4 AMR exome
AF:
0.00360
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000371
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000647
Gnomad4 OTH exome
AF:
0.00561
GnomAD4 genome
AF:
0.0266
AC:
4051
AN:
152248
Hom.:
188
Cov.:
32
AF XY:
0.0259
AC XY:
1926
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0925
Gnomad4 AMR
AF:
0.0102
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.0166
Alfa
AF:
0.00917
Hom.:
34
Bravo
AF:
0.0302
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Apr 30, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.38
DANN
Benign
0.84

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs16861392; hg19: chr1-183617371; API