rs489574

chr11-65775268-G-A

Variant summary

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

The NM_138368.5(AP5B1):c.*2588C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,066 control chromosomes in the GnomAD database, including 6,413 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 0.28 (6413 hom., cov: 32)
• Consequence: AP5B1 NM_138368.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.934

Genes affected

AP5B1 (HGNC:25104): (adaptor related protein complex 5 subunit beta 1) Involved in endosomal transport. Located in lysosomal membrane. Part of AP-type membrane coat adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP5B1	NM_138368.5	c.*2588C>T		3_prime_UTR_variant	2/2	ENST00000532090.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP5B1	ENST00000532090.3	c.*2588C>T		3_prime_UTR_variant	2/2	1	NM_138368.5	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43093 AN: 151948 Hom.: 6413 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.283 AC: 43105 AN: 152066 Hom.: 6413 Cov.: 32 AF XY: 0.277 AC XY: 20624 AN XY: 74328

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.292

Alfa AF: 0.329 Hom.: 13726

Bravo AF: 0.284

Asia WGS AF: 0.278 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.7
Dann	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs489574; hg19: chr11-65542739;