rs7603262

Variant names:

• chr2-223771773-A-C
• rs7603262
• NM_001039569.2:c.291+4128T>G

Variant summary

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

The NM_001039569.2(AP1S3):​c.291+4128T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,152 control chromosomes in the GnomAD database, including 8,407 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 0.26 (8407 hom., cov: 33)
• Consequence: AP1S3 NM_001039569.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.975

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]

ENSG00000286239 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP1S3	NM_001039569.2	c.291+4128T>G		intron_variant	Intron 3 of 4	ENST00000396654.7	NP_001034658.1
AP1S3	XM_011510600.4	c.291+4128T>G		intron_variant	Intron 3 of 3		XP_011508902.1
AP1S3	NR_110905.2	n.462+1540T>G		intron_variant	Intron 4 of 5
AP1S3	NR_110906.2	n.314+5918T>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1S3	ENST00000396654.7	c.291+4128T>G		intron_variant	Intron 3 of 4	2	NM_001039569.2	ENSP00000379891.2
ENSG00000286239	ENST00000650969.1	n.*1255+4128T>G		intron_variant	Intron 15 of 16			ENSP00000498456.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39724 AN: 152034 Hom.: 8382 Cov.: 33

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0832

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.262 AC: 39803 AN: 152152 Hom.: 8407 Cov.: 33 AF XY: 0.266 AC XY: 19822 AN XY: 74396

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.0832

Gnomad4 OTH AF: 0.240

Alfa AF: 0.144 Hom.: 1549

Bravo AF: 0.294

Asia WGS AF: 0.422 AC: 1469 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.0
DANN	Benign	0.75

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: rs7603262; hg19: chr2-224636490;