Genetic Variant NM_001300942.2:c.1730-14C>T (chr11-76523141-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_001300942.2(EMSY):c.1730-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 1,599,846 control chromosomes in the GnomAD database, including 1,436 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 0.040 ( 143 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1293 hom. )

Consequence

EMSY
NM_001300942.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.353

Publications

9 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

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0396 (6035/152226) while in subpopulation AMR AF = 0.051 (779/15278). AF 95% confidence interval is 0.048. There are 143 homozygotes in GnomAd4. There are 2854 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 6035 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMSY	NM_001300942.2 link	c.1730-14C>T		intron_variant	Intron 12 of 21	ENST00000695367.1	NP_001287871.1	Q7Z589-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMSY	ENST00000695367.1 link	c.1730-14C>T		intron_variant	Intron 12 of 21		NM_001300942.2	ENSP00000511840.1		Q7Z589-7

Frequencies

GnomAD3 genomes

AF:

0.0396

AC:

6018

AN:

152108

Hom.:

142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0411

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0511

Gnomad ASJ

AF:

0.0326

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0161

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0452

Gnomad OTH

AF:

0.0469

GnomAD2 exomes

AF:

0.0342

AC:

8161

AN:

238458

AF XY:

0.0342

show subpopulations

Gnomad AFR exome

AF:

0.0421

Gnomad AMR exome

AF:

0.0319

Gnomad ASJ exome

AF:

0.0394

Gnomad EAS exome

AF:

0.000396

Gnomad FIN exome

AF:

0.0155

Gnomad NFE exome

AF:

0.0460

Gnomad OTH exome

AF:

0.0408

GnomAD4 exome

AF:

0.0402

AC:

58231

AN:

1447620

Hom.:

1293

Cov.:

AF XY:

0.0397

AC XY:

28568

AN XY:

720212

show subpopulations

African (AFR)

AF:

0.0450

AC:

1459

AN:

32416

American (AMR)

AF:

0.0333

AC:

1365

AN:

40960

Ashkenazi Jewish (ASJ)

AF:

0.0364

AC:

925

AN:

25388

East Asian (EAS)

AF:

0.000151

AC:

AN:

39608

South Asian (SAS)

AF:

0.0192

AC:

1603

AN:

83362

European-Finnish (FIN)

AF:

0.0174

AC:

924

AN:

53120

Middle Eastern (MID)

AF:

0.0424

AC:

241

AN:

5678

European-Non Finnish (NFE)

AF:

0.0445

AC:

49316

AN:

1107424

Other (OTH)

AF:

0.0401

AC:

2392

AN:

59664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

2529

5058

7588

10117

12646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1818

3636

5454

7272

9090

<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:

0.0396

AC:

6035

AN:

152226

Hom.:

143

Cov.:

AF XY:

0.0383

AC XY:

2854

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0414

AC:

1718

AN:

41518

American (AMR)

AF:

0.0510

AC:

779

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0326

AC:

113

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.0166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0120

AC:

127

AN:

10608

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0452

AC:

3073

AN:

68022

Other (OTH)

AF:

0.0464

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

295

591

886

1182

1477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0405

Hom.:

Bravo

AF:

0.0420

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over