Variant 1-183647821-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_203454.3(APOBEC4):c.961A>G(p.Asn321Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00244 in 1,614,220 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 46 hom. )

Consequence

APOBEC4
NM_203454.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.36

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]

APOBEC4 links:

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]

RGL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003106892).

BP6

Variant 1-183647821-T-C is Benign according to our data. Variant chr1-183647821-T-C is described in ClinVar as [Benign]. Clinvar id is 783956.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 = 0.013 (1983/152330) while in subpopulation AFR AF= 0.0457 (1900/41568). AF 95% confidence interval is 0.044. There are 49 homozygotes in gnomad4. There are 913 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC4	NM_203454.3 linkuse as main transcript	c.961A>G	p.Asn321Asp	missense_variant	2/2	ENST00000308641.6	NP_982279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC4	ENST00000308641.6 linkuse as main transcript	c.961A>G	p.Asn321Asp	missense_variant	2/2	1	NM_203454.3	ENSP00000310622	P1
RGL1	ENST00000304685.8 linkuse as main transcript	c.-33+11320T>C		intron_variant		1		ENSP00000303192		Q9NZL6-2
APOBEC4	ENST00000481562.1 linkuse as main transcript	n.246-24A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1979

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0457

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:

0.00765

GnomAD3 exomes

AF:

0.00331

AC:

832

AN:

251482

Hom.:

AF XY:

0.00258

AC XY:

350

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0469

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:

0.0000527

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.00134

AC:

1960

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

821

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0501

Gnomad4 AMR exome

AF:

0.00163

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:

0.0000279

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.0130

AC:

1983

AN:

152330

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

913

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0457

Gnomad4 AMR

AF:

0.00418

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:

0.00757

Alfa

AF:

0.00212

Hom.:

Bravo

AF:

0.0154

ESP6500AA

AF:

0.0481

AC:

212

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00414

AC:

503

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.10

Sift

Benign

0.10

Sift4G

Benign

0.21

Polyphen

0.99

Vest4

0.24

MVP

0.23

MPC

0.45

ClinPred

0.027

GERP RS

5.2

Varity_R

0.27

gMVP

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over