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GeneBe

11-76546171-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001300942.2(EMSY):c.3693T>C(p.Thr1231=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,613,946 control chromosomes in the GnomAD database, including 74,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 5842 hom., cov: 32)
Exomes 𝑓: 0.30 ( 68731 hom. )

Consequence

EMSY
NM_001300942.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.884
Variant links:
Genes affected
EMSY (HGNC:18071): (EMSY transcriptional repressor, BRCA2 interacting) Predicted to enable identical protein binding activity. Predicted to be involved in DNA repair; chromatin organization; and regulation of transcription, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-76546171-T-C is Benign according to our data. Variant chr11-76546171-T-C is described in ClinVar as [Benign]. Clinvar id is 3060664.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=0.884 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EMSYNM_001300942.2 linkuse as main transcriptc.3693T>C p.Thr1231= synonymous_variant 21/22 ENST00000695367.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EMSYENST00000695367.1 linkuse as main transcriptc.3693T>C p.Thr1231= synonymous_variant 21/22 NM_001300942.2 Q7Z589-7

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.270
AC:
41053
AN:
152010
Hom.:
5838
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.209
Gnomad AMI
AF:
0.460
Gnomad AMR
AF:
0.206
Gnomad ASJ
AF:
0.383
Gnomad EAS
AF:
0.129
Gnomad SAS
AF:
0.230
Gnomad FIN
AF:
0.338
Gnomad MID
AF:
0.231
Gnomad NFE
AF:
0.316
Gnomad OTH
AF:
0.281
GnomAD3 exomes
AF:
0.267
AC:
67132
AN:
251174
Hom.:
9915
AF XY:
0.271
AC XY:
36830
AN XY:
135734
show subpopulations
Gnomad AFR exome
AF:
0.209
Gnomad AMR exome
AF:
0.153
Gnomad ASJ exome
AF:
0.389
Gnomad EAS exome
AF:
0.122
Gnomad SAS exome
AF:
0.239
Gnomad FIN exome
AF:
0.326
Gnomad NFE exome
AF:
0.318
Gnomad OTH exome
AF:
0.290
GnomAD4 exome
AF:
0.302
AC:
441176
AN:
1461818
Hom.:
68731
Cov.:
40
AF XY:
0.301
AC XY:
219014
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.203
Gnomad4 AMR exome
AF:
0.159
Gnomad4 ASJ exome
AF:
0.391
Gnomad4 EAS exome
AF:
0.138
Gnomad4 SAS exome
AF:
0.242
Gnomad4 FIN exome
AF:
0.326
Gnomad4 NFE exome
AF:
0.318
Gnomad4 OTH exome
AF:
0.294
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.270
AC:
41060
AN:
152128
Hom.:
5842
Cov.:
32
AF XY:
0.269
AC XY:
19993
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.209
Gnomad4 AMR
AF:
0.206
Gnomad4 ASJ
AF:
0.383
Gnomad4 EAS
AF:
0.128
Gnomad4 SAS
AF:
0.230
Gnomad4 FIN
AF:
0.338
Gnomad4 NFE
AF:
0.316
Gnomad4 OTH
AF:
0.278
Alfa
AF:
0.302
Hom.:
4935
Bravo
AF:
0.259
Asia WGS
AF:
0.189
AC:
658
AN:
3478
EpiCase
AF:
0.318
EpiControl
AF:
0.312

ClinVar

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

Submissions by phenotype

EMSY-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 27, 2021This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
6.4
Dann
Benign
0.63

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: rs3753051; hg19: chr11-76257215; COSMIC: COSV58258432; COSMIC: COSV58258432; API