rs11625658

Variant names:

• chr14-100257240-C-A
• rs11625658
• NM_003403.5:c.680-5064C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-100257240-C-A
• chr14-100257240-C-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.680-5064C>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
• Publications: 3 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):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Gabriele de Vries syndrome

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

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YY1	NM_003403.5	MANE Select	c.680-5064C>A		intron	N/A	NP_003394.1	P25490

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YY1	ENST00000262238.10	TSL:1 MANE Select	c.680-5064C>A		intron	N/A	ENSP00000262238.4	P25490
	YY1	ENST00000554804.1	TSL:3	c.164-5064C>A		intron	N/A	ENSP00000452225.1	H0YJV7
	YY1	ENST00000704485.1		c.-83-5064C>A		intron	N/A	ENSP00000515913.1	A0A994J726

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

African (AFR) AF: 0.236 AC: 9792 AN: 41504

American (AMR) AF: 0.227 AC: 3468 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3468

East Asian (EAS) AF: 0.211 AC: 1093 AN: 5170

South Asian (SAS) AF: 0.265 AC: 1276 AN: 4814

European-Finnish (FIN) AF: 0.334 AC: 3528 AN: 10566

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.253 AC: 17182 AN: 67992

Other (OTH) AF: 0.270 AC: 571 AN: 2114

Alfa AF: 0.251 Hom.: 1766

Bravo AF: 0.243

Asia WGS AF: 0.224 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.39
DANN	Benign	0.56
PhyloP100		-0.084
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: rs11625658; hg19: chr14-100723577;