chr11-45961406-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001352027.3(PHF21A):​c.996+3909A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,064 control chromosomes in the GnomAD database, including 22,522 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 0.51 ( 22522 hom., cov: 32)

Consequence

PHF21A
NM_001352027.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0550

Publications

3 publications found
Variant links:
Genes affected
PHF21A (HGNC:24156): (PHD finger protein 21A) The PHF21A gene encodes BHC80, a component of a BRAF35 (MIM 605535)/histone deacetylase (HDAC; see MIM 601241) complex (BHC) that mediates repression of neuron-specific genes through the cis-regulatory element known as repressor element-1 (RE1) or neural restrictive silencer (NRS) (Hakimi et al., 2002 [PubMed 12032298]).[supplied by OMIM, Nov 2010]
PHF21A Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • Potocki-Shaffer syndrome
    Inheritance: AD Classification: STRONG Submitted by: G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PHF21ANM_001352027.3 linkc.996+3909A>C intron_variant Intron 10 of 18 ENST00000676320.1 NP_001338956.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PHF21AENST00000676320.1 linkc.996+3909A>C intron_variant Intron 10 of 18 NM_001352027.3 ENSP00000502222.1 Q96BD5-3

Frequencies

GnomAD3 genomes
AF:
0.508
AC:
77115
AN:
151944
Hom.:
22523
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.230
Gnomad AMI
AF:
0.625
Gnomad AMR
AF:
0.532
Gnomad ASJ
AF:
0.736
Gnomad EAS
AF:
0.174
Gnomad SAS
AF:
0.567
Gnomad FIN
AF:
0.628
Gnomad MID
AF:
0.631
Gnomad NFE
AF:
0.658
Gnomad OTH
AF:
0.556
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.507
AC:
77119
AN:
152064
Hom.:
22522
Cov.:
32
AF XY:
0.507
AC XY:
37669
AN XY:
74330
show subpopulations
African (AFR)
AF:
0.229
AC:
9511
AN:
41492
American (AMR)
AF:
0.531
AC:
8116
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.736
AC:
2551
AN:
3468
East Asian (EAS)
AF:
0.173
AC:
899
AN:
5182
South Asian (SAS)
AF:
0.566
AC:
2730
AN:
4820
European-Finnish (FIN)
AF:
0.628
AC:
6619
AN:
10536
Middle Eastern (MID)
AF:
0.622
AC:
183
AN:
294
European-Non Finnish (NFE)
AF:
0.659
AC:
44757
AN:
67964
Other (OTH)
AF:
0.561
AC:
1183
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1697
3394
5091
6788
8485
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
662
1324
1986
2648
3310
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.594
Hom.:
6693
Bravo
AF:
0.484
Asia WGS
AF:
0.376
AC:
1313
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
2.7
DANN
Benign
0.64
PhyloP100
0.055
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

Publications

Other links and lift over

dbSNP: rs2945999; hg19: chr11-45982957; API