chr11-65775268-G-A

Variant names:

• chr11-65775268-G-A
• rs489574
• NM_138368.5:c.*2588C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138368.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP5B1	NM_138368.5	MANE Select	c.*2588C>T		3_prime_UTR	Exon 2 of 2	NP_612377.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP5B1	ENST00000532090.3	TSL:1 MANE Select	c.*2588C>T		3_prime_UTR	Exon 2 of 2	ENSP00000454303.1

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

African (AFR) AF: 0.215 AC: 8916 AN: 41486

American (AMR) AF: 0.260 AC: 3977 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 959 AN: 3466

East Asian (EAS) AF: 0.249 AC: 1290 AN: 5172

South Asian (SAS) AF: 0.248 AC: 1193 AN: 4820

European-Finnish (FIN) AF: 0.248 AC: 2618 AN: 10570

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23080 AN: 67966

Other (OTH) AF: 0.292 AC: 614 AN: 2100

Alfa AF: 0.320 Hom.: 23386

Bravo AF: 0.284

Asia WGS AF: 0.278 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.61
PhyloP100		0.93

Splicing

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

Other links and lift over

dbSNP: rs489574; hg19: chr11-65542739;