1-113905154-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000369564.6(AP4B1):c.-289G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 333,676 control chromosomes in the GnomAD database, including 87,921 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.76 (44856 hom., cov: 33)
  • Exomes 𝑓: 0.68 (43065 hom.)
• Consequence: AP4B1 ENST00000369564.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.09

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-113905154-C-G is Benign according to our data. Variant chr1-113905154-C-G is described in ClinVar as [Benign]. Clinvar id is 1278004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLRE1B	NM_001319947.2	c.-330-315C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP4B1	ENST00000369564.6	c.-289G>C		5_prime_UTR_variant	1/10	5
AP4B1	ENST00000713590.1	c.-76-361G>C		intron_variant				P1
DCLRE1B	ENST00000697125.1	n.91-315C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115388 AN: 152066 Hom.: 44802 Cov.: 33

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.734

GnomAD4 exome AF: 0.682 AC: 123707 AN: 181492 Hom.: 43065 Cov.: 0 AF XY: 0.669 AC XY: 65051 AN XY: 97190

Gnomad4 AFR exome AF: 0.943

Gnomad4 AMR exome AF: 0.699

Gnomad4 ASJ exome AF: 0.681

Gnomad4 EAS exome AF: 0.843

Gnomad4 SAS exome AF: 0.580

Gnomad4 FIN exome AF: 0.707

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.702

GnomAD4 genome AF: 0.759 AC: 115498 AN: 152184 Hom.: 44856 Cov.: 33 AF XY: 0.757 AC XY: 56314 AN XY: 74364

Gnomad4 AFR AF: 0.935

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.734

Alfa AF: 0.665 Hom.: 2234

Bravo AF: 0.771

Asia WGS AF: 0.713 AC: 2480 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	11
Dann	Benign	0.47

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: rs1217398; hg19: chr1-114447776;