22-29381302-A-G

Variant names:

• chr22-29381302-A-G
• rs5752905
• NM_001127.4:c.-28+7122T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127.4(AP1B1):​c.-28+7122T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,932 control chromosomes in the GnomAD database, including 10,397 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 0.35 (10397 hom., cov: 32)
• Consequence: AP1B1 NM_001127.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• ichthyosiform erythroderma, corneal involvement, and hearing loss

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, PanelApp Australia
• MEDNIK syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000290778 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP1B1	NM_001127.4	c.-28+7122T>C		intron_variant	Intron 1 of 22	ENST00000357586.7	NP_001118.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1B1	ENST00000357586.7	c.-28+7122T>C		intron_variant	Intron 1 of 22	1	NM_001127.4	ENSP00000350199.2

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53606 AN: 151816 Hom.: 10359 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.353 AC: 53697 AN: 151932 Hom.: 10397 Cov.: 32 AF XY: 0.360 AC XY: 26697 AN XY: 74252

African (AFR) AF: 0.465 AC: 19238 AN: 41402

American (AMR) AF: 0.269 AC: 4113 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 840 AN: 3466

East Asian (EAS) AF: 0.666 AC: 3448 AN: 5178

South Asian (SAS) AF: 0.406 AC: 1951 AN: 4800

European-Finnish (FIN) AF: 0.416 AC: 4386 AN: 10542

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18757 AN: 67962

Other (OTH) AF: 0.312 AC: 659 AN: 2110

Alfa AF: 0.249 Hom.: 886

Bravo AF: 0.347

Asia WGS AF: 0.556 AC: 1936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.46
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5752905; hg19: chr22-29777291;