chr22-29328803-T-C

Position:

• chr22-29328803-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001127.4(AP1B1):​c.*18A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 1,596,106 control chromosomes in the GnomAD database, including 1,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (398 hom., cov: 33)
  • Exomes 𝑓: 0.026 (842 hom.)
• Consequence: AP1B1 NM_001127.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.44

Genes affected

AP1B1 (HGNC:554): (adaptor related protein complex 1 subunit beta 1) Adaptor protein complex 1 is found at the cytoplasmic face of coated vesicles located at the Golgi complex, where it mediates both the recruitment of clathrin to the membrane and the recognition of sorting signals within the cytosolic tails of transmembrane receptors. This complex is a heterotetramer composed of two large, one medium, and one small adaptin subunit. The protein encoded by this gene serves as one of the large subunits of this complex and is a member of the adaptin protein family. This gene is a candidate meningioma gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 22-29328803-T-C is Benign according to our data. Variant chr22-29328803-T-C is described in ClinVar as [Benign]. Clinvar id is 1266233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP1B1	NM_001127.4	c.*18A>G		3_prime_UTR_variant	23/23	ENST00000357586.7	NP_001118.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP1B1	ENST00000357586.7	c.*18A>G		3_prime_UTR_variant	23/23	1	NM_001127.4	ENSP00000350199	P4

Frequencies

GnomAD3 genomes AF: 0.0530 AC: 8013 AN: 151204 Hom.: 396 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0265

Gnomad ASJ AF: 0.00839

Gnomad EAS AF: 0.00952

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0387

GnomAD3 exomes AF: 0.0289 AC: 6454 AN: 223512 Hom.: 203 AF XY: 0.0279 AC XY: 3360 AN XY: 120280

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.0177

Gnomad ASJ exome AF: 0.00986

Gnomad EAS exome AF: 0.00953

Gnomad SAS exome AF: 0.0439

Gnomad FIN exome AF: 0.0185

Gnomad NFE exome AF: 0.0196

Gnomad OTH exome AF: 0.0255

GnomAD4 exome AF: 0.0260 AC: 37571 AN: 1444784 Hom.: 842 Cov.: 30 AF XY: 0.0261 AC XY: 18711 AN XY: 717054

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0196

Gnomad4 ASJ exome AF: 0.00990

Gnomad4 EAS exome AF: 0.0100

Gnomad4 SAS exome AF: 0.0426

Gnomad4 FIN exome AF: 0.0185

Gnomad4 NFE exome AF: 0.0223

Gnomad4 OTH exome AF: 0.0325

GnomAD4 genome AF: 0.0531 AC: 8036 AN: 151322 Hom.: 398 Cov.: 33 AF XY: 0.0531 AC XY: 3924 AN XY: 73890

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0265

Gnomad4 ASJ AF: 0.00839

Gnomad4 EAS AF: 0.00974

Gnomad4 SAS AF: 0.0464

Gnomad4 FIN AF: 0.0193

Gnomad4 NFE AF: 0.0207

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0334 Hom.: 35

Bravo AF: 0.0575

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.046
DANN	Benign	0.46

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: rs6006095; hg19: chr22-29724792;