Variant 22-29331877-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001127.4(AP1B1):c.2349G>A(p.Ala783Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,612,808 control chromosomes in the GnomAD database, including 251,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20796 hom., cov: 32)

Exomes 𝑓: 0.56 ( 230254 hom. )

Consequence

AP1B1
NM_001127.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.15

Variant links:

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]

AP1B1 links:

AP1B1 (HGNC:):

AP1B1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 22-29331877-C-T is Benign according to our data. Variant chr22-29331877-C-T is described in ClinVar as [Benign]. Clinvar id is 1192401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP1B1	NM_001127.4 linkuse as main transcript	c.2349G>A	p.Ala783Ala	synonymous_variant	18/23	ENST00000357586.7	NP_001118.3	Q10567-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP1B1	ENST00000357586.7 linkuse as main transcript	c.2349G>A	p.Ala783Ala	synonymous_variant	18/23	1	NM_001127.4	ENSP00000350199.2		Q10567-1

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

78908

AN:

151814

Hom.:

20777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.449

Gnomad AMI

AF:

0.538

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.681

Gnomad SAS

AF:

0.526

Gnomad FIN

AF:

0.583

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.522

GnomAD3 exomes

AF:

0.539

AC:

134695

AN:

249986

Hom.:

37027

AF XY:

0.541

AC XY:

73125

AN XY:

135188

show subpopulations

Gnomad AFR exome

AF:

0.443

Gnomad AMR exome

AF:

0.455

Gnomad ASJ exome

AF:

0.489

Gnomad EAS exome

AF:

0.697

Gnomad SAS exome

AF:

0.511

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.557

Gnomad OTH exome

AF:

0.534

GnomAD4 exome

AF:

0.559

AC:

816519

AN:

1460876

Hom.:

230254

Cov.:

AF XY:

0.557

AC XY:

404566

AN XY:

726732

show subpopulations

Gnomad4 AFR exome

AF:

0.446

Gnomad4 AMR exome

AF:

0.451

Gnomad4 ASJ exome

AF:

0.491

Gnomad4 EAS exome

AF:

0.684

Gnomad4 SAS exome

AF:

0.513

Gnomad4 FIN exome

AF:

0.581

Gnomad4 NFE exome

AF:

0.568

Gnomad4 OTH exome

AF:

0.541

GnomAD4 genome

AF:

0.520

AC:

78969

AN:

151932

Hom.:

20796

Cov.:

AF XY:

0.519

AC XY:

38501

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.449

Gnomad4 AMR

AF:

0.455

Gnomad4 ASJ

AF:

0.504

Gnomad4 EAS

AF:

0.682

Gnomad4 SAS

AF:

0.526

Gnomad4 FIN

AF:

0.583

Gnomad4 NFE

AF:

0.556

Gnomad4 OTH

AF:

0.528

Alfa

AF:

0.518

Hom.:

12039

Bravo

AF:

0.509

Asia WGS

AF:

0.618

AC:

2152

AN:

3478

EpiCase

AF:

0.548

EpiControl

AF:

0.547

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Oct 18, 2018	- -

Autosomal recessive keratitis-ichthyosis-deafness syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.68

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over