1-113901972-T-G

Variant summary

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

The NM_001253852.3(AP4B1):​c.339-87A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,487,696 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 66 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 56 hom. )

Consequence

AP4B1
NM_001253852.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.619
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]

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=-0.88).
BP6
Variant 1-113901972-T-G is Benign according to our data. Variant chr1-113901972-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1219482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AP4B1NM_001253852.3 linkuse as main transcriptc.339-87A>C intron_variant ENST00000369569.6 NP_001240781.1 Q9Y6B7-1A0A024R0J5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AP4B1ENST00000369569.6 linkuse as main transcriptc.339-87A>C intron_variant 1 NM_001253852.3 ENSP00000358582.1 Q9Y6B7-1

Frequencies

GnomAD3 genomes
AF:
0.0147
AC:
2240
AN:
152140
Hom.:
66
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0507
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00609
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.0129
GnomAD4 exome
AF:
0.00161
AC:
2146
AN:
1335436
Hom.:
56
Cov.:
20
AF XY:
0.00132
AC XY:
888
AN XY:
670732
show subpopulations
Gnomad4 AFR exome
AF:
0.0543
Gnomad4 AMR exome
AF:
0.00281
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000971
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000155
Gnomad4 OTH exome
AF:
0.00304
GnomAD4 genome
AF:
0.0147
AC:
2243
AN:
152260
Hom.:
66
Cov.:
32
AF XY:
0.0139
AC XY:
1034
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0506
Gnomad4 AMR
AF:
0.00608
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.0128
Alfa
AF:
0.0168
Hom.:
6
Bravo
AF:
0.0162

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingGeneDxJul 05, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.062
DANN
Benign
0.64

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

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

Other links and lift over

dbSNP: rs12079716; hg19: chr1-114444594; API