22-39103599-T-C

Position:

• chr22-39103599-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.544-90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,396,454 control chromosomes in the GnomAD database, including 74,710 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 (8292 hom., cov: 33)
  • Exomes 𝑓: 0.32 (66418 hom.)
• Consequence: APOBEC3H NM_181773.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3H	NM_181773.5	c.544-90T>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.544-90T>C		intron_variant		3	NM_181773.5	ENSP00000411754.3
APOBEC3H	ENST00000348946.8	c.544-93T>C		intron_variant		1		ENSP00000216123.5
APOBEC3H	ENST00000401756.5	c.*35-90T>C		intron_variant		3		ENSP00000385741.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49888 AN: 152024 Hom.: 8284 Cov.: 33

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.322 AC: 400435 AN: 1244312 Hom.: 66418 AF XY: 0.328 AC XY: 206214 AN XY: 629604

Gnomad4 AFR exome AF: 0.314

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.256

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.421

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.328 AC: 49932 AN: 152142 Hom.: 8292 Cov.: 33 AF XY: 0.332 AC XY: 24675 AN XY: 74368

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.291

Alfa AF: 0.325 Hom.: 12319

Bravo AF: 0.311

Asia WGS AF: 0.321 AC: 1119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.68

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: rs139314; hg19: chr22-39499604; COSMIC: COSV62378678; COSMIC: COSV62378678;