chr11-45935741-TAAAAA-T

Position:

• chr11-45935741-TAAAAA-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001352027.3(PHF21A):​c.1685-7_1685-3delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 515,874 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000065 (0 hom., cov: 0)
  • Exomes 𝑓: 0.017 (0 hom.)
• Consequence: PHF21A NM_001352027.3 splice_region, intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.62

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 11-45935741-TAAAAA-T is Benign according to our data. Variant chr11-45935741-TAAAAA-T is described in ClinVar as [Benign]. Clinvar id is 3041678.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0174 (7082/407538) while in subpopulation AMR AF= 0.0199 (329/16564). AF 95% confidence interval is 0.0181. There are 0 homozygotes in gnomad4_exome. There are 3803 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF21A	NM_001352027.3	c.1685-7_1685-3delTTTTT		splice_region_variant, intron_variant		ENST00000676320.1	NP_001338956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF21A	ENST00000676320.1	c.1685-7_1685-3delTTTTT		splice_region_variant, intron_variant			NM_001352027.3	ENSP00000502222.1

Frequencies

GnomAD3 genomes AF: 0.0000646 AC: 7 AN: 108336 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000388

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000186

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0148 AC: 716 AN: 48272 Hom.: 0 AF XY: 0.0157 AC XY: 398 AN XY: 25422

Gnomad AFR exome AF: 0.00924

Gnomad AMR exome AF: 0.0231

Gnomad ASJ exome AF: 0.0133

Gnomad EAS exome AF: 0.0185

Gnomad SAS exome AF: 0.0142

Gnomad FIN exome AF: 0.00853

Gnomad NFE exome AF: 0.0132

Gnomad OTH exome AF: 0.0195

GnomAD4 exome AF: 0.0174 AC: 7082 AN: 407538 Hom.: 0 AF XY: 0.0177 AC XY: 3803 AN XY: 215236

Gnomad4 AFR exome AF: 0.0159

Gnomad4 AMR exome AF: 0.0199

Gnomad4 ASJ exome AF: 0.0179

Gnomad4 EAS exome AF: 0.0168

Gnomad4 SAS exome AF: 0.0163

Gnomad4 FIN exome AF: 0.0164

Gnomad4 NFE exome AF: 0.0175

Gnomad4 OTH exome AF: 0.0181

GnomAD4 genome AF: 0.0000646 AC: 7 AN: 108336 Hom.: 0 Cov.: 0 AF XY: 0.0000598 AC XY: 3 AN XY: 50148

Gnomad4 AFR AF: 0.0000350

Gnomad4 AMR AF: 0.000388

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.0000186

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PHF21A-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 13, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35995547; hg19: chr11-45957292;