2-223696612-C-T

Position:

• chr2-223696612-C-T

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, non coding transcript 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, non_coding_transcript
• 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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP1S3	ENST00000699384.1	n.1032-2070G>A		intron_variant, non_coding_transcript_variant

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;