dbSNP rs4245443: EMSY:c.1153+40A>G (chr11-76472880-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001300942.2(EMSY):c.1153+40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,597,998 control chromosomes in the GnomAD database, including 290,803 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 0.55 ( 24111 hom., cov: 32)

Exomes 𝑓: 0.60 ( 266692 hom. )

Consequence

EMSY
NM_001300942.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.70

Publications

21 publications found

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

new If you want to explore the variant's impact on the transcript NM_001300942.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300942.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EMSY	NM_001300942.2	MANE Select	c.1153+40A>G	intron	N/A	NP_001287871.1	Q7Z589-7
EMSY	NM_001300943.2		c.1111+40A>G	intron	N/A	NP_001287872.1	Q7Z589-5
EMSY	NM_001300944.2		c.1153+40A>G	intron	N/A	NP_001287873.1	Q7Z589-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EMSY	ENST00000695367.1	MANE Select	c.1153+40A>G	intron	N/A	ENSP00000511840.1	Q7Z589-7
EMSY	ENST00000524767.5	TSL:1	c.1153+40A>G	intron	N/A	ENSP00000433205.1	Q7Z589-7
EMSY	ENST00000525038.5	TSL:1	c.1153+40A>G	intron	N/A	ENSP00000436968.1	Q7Z589-4

Frequencies

GnomAD3 genomes

AF:

0.551

AC:

83717

AN:

151956

Hom.:

24089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.385

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.667

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.725

Gnomad SAS

AF:

0.674

Gnomad FIN

AF:

0.605

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.601

Gnomad OTH

AF:

0.547

GnomAD2 exomes

AF:

0.622

AC:

153097

AN:

246050

AF XY:

0.624

show subpopulations

Gnomad AFR exome

AF:

0.378

Gnomad AMR exome

AF:

0.775

Gnomad ASJ exome

AF:

0.441

Gnomad EAS exome

AF:

0.722

Gnomad FIN exome

AF:

0.613

Gnomad NFE exome

AF:

0.599

Gnomad OTH exome

AF:

0.601

GnomAD4 exome

AF:

0.604

AC:

872928

AN:

1445924

Hom.:

266692

Cov.:

AF XY:

0.606

AC XY:

434309

AN XY:

717262

show subpopulations

African (AFR)

AF:

0.375

AC:

12411

AN:

33062

American (AMR)

AF:

0.763

AC:

33891

AN:

44394

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

11435

AN:

25778

East Asian (EAS)

AF:

0.717

AC:

28220

AN:

39380

South Asian (SAS)

AF:

0.672

AC:

57334

AN:

85296

European-Finnish (FIN)

AF:

0.613

AC:

32541

AN:

53054

Middle Eastern (MID)

AF:

0.551

AC:

2675

AN:

4852

European-Non Finnish (NFE)

AF:

0.599

AC:

659456

AN:

1100478

Other (OTH)

AF:

0.586

AC:

34965

AN:

59630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

17405

34810

52214

69619

87024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18102

36204

54306

72408

90510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.551

AC:

83778

AN:

152074

Hom.:

24111

Cov.:

AF XY:

0.555

AC XY:

41259

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.386

AC:

15993

AN:

41468

American (AMR)

AF:

0.668

AC:

10213

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1554

AN:

3466

East Asian (EAS)

AF:

0.725

AC:

3761

AN:

5188

South Asian (SAS)

AF:

0.674

AC:

3246

AN:

4818

European-Finnish (FIN)

AF:

0.605

AC:

6384

AN:

10552

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.601

AC:

40851

AN:

67978

Other (OTH)

AF:

0.546

AC:

1153

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1890

3780

5671

7561

9451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.587

Hom.:

45825

Bravo

AF:

0.548

Asia WGS

AF:

0.643

AC:

2234

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

0.034

(source)

DANN

Benign

0.44

PhyloP100

-3.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over