14-100259101-A-G

Variant names:

• chr14-100259101-A-G
• rs4905941
• NM_003403.5:c.680-3203A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003403.5(YY1):​c.680-3203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,160 control chromosomes in the GnomAD database, including 6,845 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 0.30 (6845 hom., cov: 33)
• Consequence: YY1 NM_003403.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• Publications: 4 publications found

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]

YY1 Gene-Disease associations (from GenCC):

• Gabriele de Vries syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003403.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YY1	NM_003403.5	MANE Select	c.680-3203A>G		intron	N/A	NP_003394.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YY1	ENST00000262238.10	TSL:1 MANE Select	c.680-3203A>G		intron	N/A	ENSP00000262238.4
	YY1	ENST00000554804.1	TSL:3	c.164-3203A>G		intron	N/A	ENSP00000452225.1
	YY1	ENST00000704485.1		c.-83-3203A>G		intron	N/A	ENSP00000515913.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44973 AN: 152042 Hom.: 6843 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.296 AC: 44985 AN: 152160 Hom.: 6845 Cov.: 33 AF XY: 0.300 AC XY: 22303 AN XY: 74386

African (AFR) AF: 0.254 AC: 10561 AN: 41518

American (AMR) AF: 0.358 AC: 5468 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 869 AN: 3470

East Asian (EAS) AF: 0.390 AC: 2015 AN: 5170

South Asian (SAS) AF: 0.529 AC: 2549 AN: 4818

European-Finnish (FIN) AF: 0.267 AC: 2829 AN: 10584

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19704 AN: 68002

Other (OTH) AF: 0.295 AC: 622 AN: 2112

Alfa AF: 0.267 Hom.: 2601

Bravo AF: 0.296

Asia WGS AF: 0.417 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.67
PhyloP100		-0.20
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

Other links and lift over

dbSNP: rs4905941; hg19: chr14-100725438;