rs139285

Variant names:

• chr22-39099775-T-C
• rs139285
• NM_181773.5:c.-7-497T>C

Variant summary

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

The NM_181773.5(APOBEC3H):​c.-7-497T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,864 control chromosomes in the GnomAD database, including 26,816 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 0.57 (26816 hom., cov: 32)
• Consequence: APOBEC3H NM_181773.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3H	NM_181773.5	c.-7-497T>C		intron_variant	Intron 1 of 4	ENST00000442487.8	NP_861438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8	c.-7-497T>C		intron_variant	Intron 1 of 4	3	NM_181773.5	ENSP00000411754.3

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85887 AN: 151744 Hom.: 26761 Cov.: 32

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.566 AC: 85998 AN: 151864 Hom.: 26816 Cov.: 32 AF XY: 0.564 AC XY: 41869 AN XY: 74228

African (AFR) AF: 0.854 AC: 35408 AN: 41464

American (AMR) AF: 0.419 AC: 6397 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1580 AN: 3468

East Asian (EAS) AF: 0.360 AC: 1849 AN: 5138

South Asian (SAS) AF: 0.480 AC: 2313 AN: 4814

European-Finnish (FIN) AF: 0.529 AC: 5580 AN: 10540

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.460 AC: 31204 AN: 67882

Other (OTH) AF: 0.500 AC: 1052 AN: 2102

Alfa AF: 0.539 Hom.: 3144

Bravo AF: 0.567

Asia WGS AF: 0.418 AC: 1459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.70
PhyloP100		-0.88
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: rs139285; hg19: chr22-39495780;