Menu
GeneBe

14-100239469-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003403.5(YY1):c.225T>C(p.His75=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,592,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 29)
Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

YY1
NM_003403.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.220
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-100239469-T-C is Benign according to our data. Variant chr14-100239469-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2644521.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.22 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 18 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
YY1NM_003403.5 linkuse as main transcriptc.225T>C p.His75= synonymous_variant 1/5 ENST00000262238.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
YY1ENST00000262238.10 linkuse as main transcriptc.225T>C p.His75= synonymous_variant 1/51 NM_003403.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000126
AC:
18
AN:
142816
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.000236
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000226
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000123
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000129
AC:
28
AN:
216794
Hom.:
0
AF XY:
0.000158
AC XY:
19
AN XY:
120046
show subpopulations
Gnomad AFR exome
AF:
0.000158
Gnomad AMR exome
AF:
0.0000919
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000120
Gnomad SAS exome
AF:
0.0000688
Gnomad FIN exome
AF:
0.0000598
Gnomad NFE exome
AF:
0.000191
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000241
AC:
350
AN:
1449958
Hom.:
0
Cov.:
33
AF XY:
0.000220
AC XY:
159
AN XY:
721154
show subpopulations
Gnomad4 AFR exome
AF:
0.0000902
Gnomad4 AMR exome
AF:
0.000136
Gnomad4 ASJ exome
AF:
0.0000772
Gnomad4 EAS exome
AF:
0.000154
Gnomad4 SAS exome
AF:
0.0000467
Gnomad4 FIN exome
AF:
0.0000206
Gnomad4 NFE exome
AF:
0.000284
Gnomad4 OTH exome
AF:
0.000184
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000126
AC:
18
AN:
142816
Hom.:
0
Cov.:
29
AF XY:
0.0000861
AC XY:
6
AN XY:
69648
show subpopulations
Gnomad4 AFR
AF:
0.000236
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000226
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000123
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000176
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023YY1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
Cadd
Benign
9.4
Dann
Benign
0.74

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs367701201; hg19: chr14-100705806; COSMIC: COSV51761419; COSMIC: COSV51761419; API