Variant chr11-76516138-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001300942.2(EMSY):c.1559-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,605,772 control chromosomes in the GnomAD database, including 312,285 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.58 ( 26440 hom., cov: 31)

Exomes 𝑓: 0.62 ( 285845 hom. )

Consequence

EMSY
NM_001300942.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001893

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.329

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]

EMSY links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-76516138-G-A is Benign according to our data. Variant chr11-76516138-G-A is described in ClinVar as [Benign]. Clinvar id is 3058884.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMSY	NM_001300942.2 linkuse as main transcript	c.1559-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000695367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMSY	ENST00000695367.1 linkuse as main transcript	c.1559-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001300942.2		Q7Z589-7

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

87968

AN:

151782

Hom.:

26411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.430

Gnomad AMI

AF:

0.490

Gnomad AMR

AF:

0.681

Gnomad ASJ

AF:

0.542

Gnomad EAS

AF:

0.820

Gnomad SAS

AF:

0.733

Gnomad FIN

AF:

0.632

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.613

Gnomad OTH

AF:

0.574

GnomAD3 exomes

AF:

0.650

AC:

159672

AN:

245470

Hom.:

53500

AF XY:

0.653

AC XY:

86538

AN XY:

132614

show subpopulations

Gnomad AFR exome

AF:

0.422

Gnomad AMR exome

AF:

0.781

Gnomad ASJ exome

AF:

0.534

Gnomad EAS exome

AF:

0.825

Gnomad SAS exome

AF:

0.723

Gnomad FIN exome

AF:

0.640

Gnomad NFE exome

AF:

0.611

Gnomad OTH exome

AF:

0.628

GnomAD4 exome

AF:

0.623

AC:

905821

AN:

1453870

Hom.:

285845

Cov.:

AF XY:

0.626

AC XY:

452430

AN XY:

723072

show subpopulations

Gnomad4 AFR exome

AF:

0.421

Gnomad4 AMR exome

AF:

0.770

Gnomad4 ASJ exome

AF:

0.535

Gnomad4 EAS exome

AF:

0.814

Gnomad4 SAS exome

AF:

0.719

Gnomad4 FIN exome

AF:

0.638

Gnomad4 NFE exome

AF:

0.611

Gnomad4 OTH exome

AF:

0.616

GnomAD4 genome

AF:

0.580

AC:

88037

AN:

151902

Hom.:

26440

Cov.:

AF XY:

0.585

AC XY:

43421

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.430

Gnomad4 AMR

AF:

0.681

Gnomad4 ASJ

AF:

0.542

Gnomad4 EAS

AF:

0.820

Gnomad4 SAS

AF:

0.733

Gnomad4 FIN

AF:

0.632

Gnomad4 NFE

AF:

0.613

Gnomad4 OTH

AF:

0.577

Alfa

AF:

0.605

Hom.:

63486

Bravo

AF:

0.575

Asia WGS

AF:

0.746

AC:

2592

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EMSY-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 10, 2022

This 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

-0.82

CADD

Benign

0.94

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over