14-100239450-GCCACCA-G

Position:

• chr14-100239450-GCCACCA-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_003403.5(YY1):​c.219_224del​(p.His79_His80del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,595,218 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000097 (0 hom.)
• Consequence: YY1 NM_003403.5 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.67

Genes affected

YY1 (HGNC:12856): (YY1 transcription factor) YY1 is a ubiquitously distributed transcription factor belonging to the GLI-Kruppel class of zinc finger proteins. The protein is involved in repressing and activating a diverse number of promoters. YY1 may direct histone deacetylases and histone acetyltransferases to a promoter in order to activate or repress the promoter, thus implicating histone modification in the function of YY1. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 14-100239450-GCCACCA-G is Benign according to our data. Variant chr14-100239450-GCCACCA-G is described in ClinVar as [Likely_benign]. Clinvar id is 2386037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YY1	NM_003403.5	c.219_224del	p.His79_His80del	inframe_deletion	1/5	ENST00000262238.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YY1	ENST00000262238.10	c.219_224del	p.His79_His80del	inframe_deletion	1/5	1	NM_003403.5	P1

Frequencies

GnomAD3 genomes AF: 0.000201 AC: 30 AN: 149510 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000406

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000238

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000122 AC: 25 AN: 205146 Hom.: 0 AF XY: 0.000114 AC XY: 13 AN XY: 113638

Gnomad AFR exome AF: 0.000171

Gnomad AMR exome AF: 0.0000631

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000702

Gnomad SAS exome AF: 0.0000352

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000908

Gnomad OTH exome AF: 0.000186

GnomAD4 exome AF: 0.0000968 AC: 140 AN: 1445592 Hom.: 0 AF XY: 0.000104 AC XY: 75 AN XY: 718318

Gnomad4 AFR exome AF: 0.000181

Gnomad4 AMR exome AF: 0.0000462

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00136

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.0000211

Gnomad4 NFE exome AF: 0.0000624

Gnomad4 OTH exome AF: 0.000100

GnomAD4 genome AF: 0.000200 AC: 30 AN: 149626 Hom.: 0 Cov.: 29 AF XY: 0.000150 AC XY: 11 AN XY: 73132

Gnomad4 AFR AF: 0.000246

Gnomad4 AMR AF: 0.0000662

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000407

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000238

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

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: rs76675246; hg19: chr14-100705787;