22-39099665-C-T

Variant names:

• chr22-39099665-C-T
• rs139284
• NM_181773.5:c.-7-607C>T

Variant summary

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

The NM_181773.5(APOBEC3H):​c.-7-607C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,076 control chromosomes in the GnomAD database, including 13,686 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 0.42 (13686 hom., cov: 32)
• Consequence: APOBEC3H NM_181773.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.686
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3H	NM_181773.5	c.-7-607C>T		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.-7-607C>T		intron_variant	Intron 1 of 4	3	NM_181773.5	ENSP00000411754.3

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63064 AN: 151956 Hom.: 13652 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.415 AC: 63156 AN: 152076 Hom.: 13686 Cov.: 32 AF XY: 0.418 AC XY: 31089 AN XY: 74358

African (AFR) AF: 0.542 AC: 22469 AN: 41466

American (AMR) AF: 0.325 AC: 4962 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3470

East Asian (EAS) AF: 0.346 AC: 1789 AN: 5174

South Asian (SAS) AF: 0.458 AC: 2211 AN: 4826

European-Finnish (FIN) AF: 0.457 AC: 4839 AN: 10596

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24549 AN: 67946

Other (OTH) AF: 0.356 AC: 749 AN: 2102

Alfa AF: 0.381 Hom.: 2131

Bravo AF: 0.406

Asia WGS AF: 0.378 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.41
PhyloP100		0.69
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: rs139284; hg19: chr22-39495670;