rs11625658

chr14-100257240-C-Achr14-100257240-C-G

Variant summary

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

The NM_003403.5(YY1):c.680-5064C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,106 control chromosomes in the GnomAD database, including 4,903 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 0.25 (4903 hom., cov: 32)
• Consequence: YY1 NM_003403.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YY1	NM_003403.5	c.680-5064C>A		intron_variant		ENST00000262238.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YY1	ENST00000262238.10	c.680-5064C>A		intron_variant		1	NM_003403.5	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38237 AN: 151988 Hom.: 4895 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.252 AC: 38256 AN: 152106 Hom.: 4903 Cov.: 32 AF XY: 0.254 AC XY: 18895 AN XY: 74352

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.270

Alfa AF: 0.252 Hom.: 971

Bravo AF: 0.243

Asia WGS AF: 0.224 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.39
Dann	Benign	0.56

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: rs11625658; hg19: chr14-100723577;