Genetic Variant NM_001349436.1:c.-144C>A (chr22-39077041-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001349436.1(APOBEC3G):c.-144C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 138,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000050 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000074 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

APOBEC3G
NM_001349436.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0400

Publications

6 publications found

Variant links:

Genes affected

APOBEC3G (HGNC:17357): (apolipoprotein B mRNA editing enzyme catalytic subunit 3G) This gene is a member of the cytidine deaminase gene family. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22. Members of the cluster encode proteins that are structurally and functionally related to the C to U RNA-editing cytidine deaminase APOBEC1. The protein encoded by this gene catalyzes site-specific deamination of both RNA and single-stranded DNA. The encoded protein has been found to be a specific inhibitor of human immunodeficiency virus-1 (HIV-1) infectivity. [provided by RefSeq, Mar 2017]

APOBEC3G links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349436.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOBEC3G	NM_001349436.1		c.-144C>A	5_prime_UTR	Exon 1 of 8	NP_001336365.1
APOBEC3G	NM_021822.4	MANE Select	c.-321C>A	upstream_gene	N/A	NP_068594.1	Q9HC16-1
APOBEC3G	NM_001349437.2		c.-368C>A	upstream_gene	N/A	NP_001336366.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOBEC3G	ENST00000407997.4	TSL:1 MANE Select	c.-321C>A	upstream_gene	N/A	ENSP00000385057.3	Q9HC16-1
APOBEC3G	ENST00000960612.1		c.-321C>A	upstream_gene	N/A	ENSP00000630671.1
APOBEC3G	ENST00000851527.1		c.-321C>A	upstream_gene	N/A	ENSP00000521586.1

Frequencies

GnomAD3 genomes

AF:

0.0000504

AC:

AN:

138758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000112

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000744

AC:

AN:

336116

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

176420

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10106

American (AMR)

AF:

0.00

AC:

AN:

14534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10390

East Asian (EAS)

AF:

0.00

AC:

AN:

22028

South Asian (SAS)

AF:

0.00

AC:

AN:

37516

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1466

European-Non Finnish (NFE)

AF:

0.000115

AC:

AN:

200824

Other (OTH)

AF:

0.000102

AC:

AN:

19544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000504

AC:

AN:

138758

Hom.:

Cov.:

AF XY:

0.0000443

AC XY:

AN XY:

67738

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37210

American (AMR)

AF:

0.00

AC:

AN:

13592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3224

East Asian (EAS)

AF:

0.00

AC:

AN:

4682

South Asian (SAS)

AF:

0.00

AC:

AN:

4494

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9918

Middle Eastern (MID)

AF:

0.00

AC:

AN:

298

European-Non Finnish (NFE)

AF:

0.000112

AC:

AN:

62572

Other (OTH)

AF:

0.00

AC:

AN:

1922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

539

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.9

(source)

DANN

Benign

0.61

PhyloP100

0.040

PromoterAI

-0.55

Under-expression

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over