2-223696612-C-T

Variant names:

• chr2-223696612-C-T
• rs734556
• ENST00000699384.1:n.1032-2070G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699384.1(AP1S3):​n.1032-2070G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 152,078 control chromosomes in the GnomAD database, including 22,191 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 0.48 (22191 hom., cov: 32)
• Consequence: AP1S3 ENST00000699384.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

AP1S3 (HGNC:18971): (adaptor related protein complex 1 subunit sigma 3) This gene encodes a member of the adaptor-related protein complex 1, sigma subunit genes. The encoded protein is a component of adaptor protein complex 1 (AP-1), one of the AP complexes involved in claathrin-mediated vesicular transport from the Golgi or endosomes. Disruption of the pathway for display of HIV-1 antigens, which prevents recognition of the virus by cytotoxic T cells, has been shown to involve the AP-1 complex (PMID: 15569716). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1S3	ENST00000699384.1	n.1032-2070G>A		intron_variant	Intron 9 of 10

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73038 AN: 151960 Hom.: 22197 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.480 AC: 73036 AN: 152078 Hom.: 22191 Cov.: 32 AF XY: 0.483 AC XY: 35907 AN XY: 74348

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.503

Alfa AF: 0.614 Hom.: 15974

Bravo AF: 0.440

Asia WGS AF: 0.398 AC: 1387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs734556; hg19: chr2-224561329;