1-113904989-T-C

Position:

• chr1-113904989-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000256658.8(AP4B1):​c.-124A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00774 in 458,258 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (22 hom., cov: 33)
  • Exomes 𝑓: 0.0075 (25 hom.)
• Consequence: AP4B1 ENST00000256658.8 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.591

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 -10 ACMG points.

• BP6: Variant 1-113904989-T-C is Benign according to our data. Variant chr1-113904989-T-C is described in ClinVar as [Benign]. Clinvar id is 1271892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00833 (1267/152106) while in subpopulation NFE AF= 0.0083 (564/67982). AF 95% confidence interval is 0.00773. There are 22 homozygotes in gnomad4. There are 748 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP4B1	NM_001253853.3	c.-293A>G		5_prime_UTR_variant	1/11
AP4B1	NM_006594.5	c.-124A>G		5_prime_UTR_variant	1/11
AP4B1	XM_011540523.4	c.-124A>G		5_prime_UTR_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP4B1	ENST00000256658.8	c.-124A>G		5_prime_UTR_variant	1/11	1		P1
AP4B1	ENST00000369564.6	c.-124A>G		5_prime_UTR_variant	1/10	5
AP4B1	ENST00000369571.3	c.-145A>G		5_prime_UTR_variant	1/11	3		P1

Frequencies

GnomAD3 genomes AF: 0.00834 AC: 1267 AN: 151988 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0566

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00830

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00745 AC: 2281 AN: 306152 Hom.: 25 Cov.: 0 AF XY: 0.00681 AC XY: 1113 AN XY: 163502

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.00257

Gnomad4 ASJ exome AF: 0.00260

Gnomad4 EAS exome AF: 0.0000552

Gnomad4 SAS exome AF: 0.000889

Gnomad4 FIN exome AF: 0.0486

Gnomad4 NFE exome AF: 0.00728

Gnomad4 OTH exome AF: 0.00651

GnomAD4 genome AF: 0.00833 AC: 1267 AN: 152106 Hom.: 22 Cov.: 33 AF XY: 0.0101 AC XY: 748 AN XY: 74366

Gnomad4 AFR AF: 0.000650

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00606

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0566

Gnomad4 NFE AF: 0.00830

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.0133 Hom.: 8

Bravo AF: 0.00342

Asia WGS AF: 0.000577 AC: 2 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

Oct 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.5
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.48		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.48		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs189306022; hg19: chr1-114447611;