1-113904943-G-A

Position:

chr1-113904943-G-A

Variant summary

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

The ENST00000256658.8(AP4B1):c.-78C>T variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 515,762 control chromosomes in the GnomAD database, including 26,127 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10921 hom., cov: 32)

Exomes 𝑓: 0.28 ( 15206 hom. )

Consequence

AP4B1
ENST00000256658.8 splice_region, 5_prime_UTR

Scores

Splicing: ADA: 0.002412

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.49

Variant links:

Genes affected

AP4B1 (HGNC:572): (adaptor related protein complex 4 subunit beta 1) This gene encodes a subunit of a heterotetrameric adapter-like complex 4 that is involved in targeting proteins from the trans-Golgi network to the endosomal-lysosomal system. Mutations in this gene are associated with cerebral palsy spastic quadriplegic type 5 (CPSQ5) disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

AP4B1 links:

DCLRE1B (HGNC:17641): (DNA cross-link repair 1B) DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1B is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000 [PubMed 10848582]).[supplied by OMIM, Mar 2008]

DCLRE1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-113904943-G-A is Benign according to our data. Variant chr1-113904943-G-A is described in ClinVar as [Benign]. Clinvar id is 380767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
AP4B1	NM_001253853.3 linkuse as main transcript	c.-247C>T	splice_region_variant, 5_prime_UTR_variant	1/11	NP_001240782.1
AP4B1	NM_006594.5 linkuse as main transcript	c.-78C>T	splice_region_variant, 5_prime_UTR_variant	1/11	NP_006585.2
AP4B1	XM_011540523.4 linkuse as main transcript	c.-78C>T	splice_region_variant, 5_prime_UTR_variant	1/10	XP_011538825.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	Appris	UniProt
AP4B1	ENST00000256658.8 linkuse as main transcript	c.-78C>T	splice_region_variant, 5_prime_UTR_variant	1/11	1	ENSP00000256658	P1	Q9Y6B7-1
AP4B1	ENST00000369564.6 linkuse as main transcript	c.-78C>T	splice_region_variant, 5_prime_UTR_variant	1/10	5	ENSP00000358577
AP4B1	ENST00000369571.3 linkuse as main transcript	c.-99C>T	5_prime_UTR_variant	1/11	3	ENSP00000358584	P1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

52960

AN:

151598

Hom.:

10902

Cov.:

show subpopulations

Gnomad AFR

AF:

0.573

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.0749

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.324

GnomAD4 exome

AF:

0.277

AC:

100915

AN:

364046

Hom.:

15206

Cov.:

AF XY:

0.277

AC XY:

53636

AN XY:

193724

show subpopulations

Gnomad4 AFR exome

AF:

0.580

Gnomad4 AMR exome

AF:

0.181

Gnomad4 ASJ exome

AF:

0.359

Gnomad4 EAS exome

AF:

0.0974

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.247

Gnomad4 NFE exome

AF:

0.285

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.349

AC:

53017

AN:

151716

Hom.:

10921

Cov.:

AF XY:

0.342

AC XY:

25325

AN XY:

74086

show subpopulations

Gnomad4 AFR

AF:

0.572

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.0750

Gnomad4 SAS

AF:

0.269

Gnomad4 FIN

AF:

0.230

Gnomad4 NFE

AF:

0.289

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.289

Hom.:

12467

Bravo

AF:

0.353

Asia WGS

AF:

0.183

AC:

638

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 12, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.43

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0024

dbscSNV1_RF

Benign

0.012

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

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