rs139296

Variant names:

• chr22-39101001-G-A
• rs139296
• NM_181773.5:c.151-236G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181773.5(APOBEC3H):​c.151-236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,978 control chromosomes in the GnomAD database, including 8,446 homozygotes. 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 0.33 (8446 hom., cov: 31)
• Consequence: APOBEC3H NM_181773.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.927
• Publications: 4 publications found

Genes affected

APOBEC3H (HGNC:24100): (apolipoprotein B mRNA editing enzyme catalytic subunit 3H) This gene encodes a member of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3 family of proteins. The encoded protein is a cytidine deaminase that has antiretroviral activity by generating lethal hypermutations in viral genomes. Polymorphisms and alternative splicing in this gene influence its antiretroviral activity and are associated with increased resistence to human immunodeficiency virus type 1 infection in certain populations. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3H	NM_181773.5	c.151-236G>A		intron_variant	Intron 2 of 4	ENST00000442487.8	NP_861438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8	c.151-236G>A		intron_variant	Intron 2 of 4	3	NM_181773.5	ENSP00000411754.3

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50334 AN: 151858 Hom.: 8435 Cov.: 31

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.332 AC: 50383 AN: 151978 Hom.: 8446 Cov.: 31 AF XY: 0.335 AC XY: 24898 AN XY: 74280

African (AFR) AF: 0.323 AC: 13403 AN: 41450

American (AMR) AF: 0.283 AC: 4314 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3472

East Asian (EAS) AF: 0.272 AC: 1404 AN: 5154

South Asian (SAS) AF: 0.432 AC: 2079 AN: 4818

European-Finnish (FIN) AF: 0.420 AC: 4443 AN: 10576

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.333 AC: 22638 AN: 67930

Other (OTH) AF: 0.297 AC: 627 AN: 2112

Alfa AF: 0.332 Hom.: 2104

Bravo AF: 0.316

Asia WGS AF: 0.320 AC: 1117 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.76
PhyloP100		0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs139296; hg19: chr22-39497006; COSMIC: COSV62379123; COSMIC: COSV62379123;