rs139285

Positions:

• chr22-39099775-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
APOBEC3H	NM_181773.5	c.-7-497T>C		intron_variant		ENST00000442487.8	NP_861438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8	c.-7-497T>C		intron_variant		3	NM_181773.5	ENSP00000411754	A2

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

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.500

Alfa AF: 0.527 Hom.: 2867

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

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

Other links and lift over

dbSNP: rs139285; hg19: chr22-39495780;