rs10501316

Positions:

• chr11-46068999-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352027.3(PHF21A):​c.153+7755G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,104 control chromosomes in the GnomAD database, including 1,643 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 0.14 (1643 hom., cov: 32)
• Consequence: PHF21A NM_001352027.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF21A	NM_001352027.3	c.153+7755G>A		intron_variant		ENST00000676320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF21A	ENST00000676320.1	c.153+7755G>A		intron_variant			NM_001352027.3	P3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21048 AN: 151986 Hom.: 1644 Cov.: 32

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0992

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.138 AC: 21059 AN: 152104 Hom.: 1643 Cov.: 32 AF XY: 0.139 AC XY: 10301 AN XY: 74354

Gnomad4 AFR AF: 0.0893

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0992

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.119

Alfa AF: 0.159 Hom.: 2716

Bravo AF: 0.129

Asia WGS AF: 0.136 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.45

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: rs10501316; hg19: chr11-46090550;