rs2508740

Variant names:

• chr11-76516138-G-A
• rs2508740
• NM_001300942.2:c.1559-4G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-76516138-G-A
• chr11-76516138-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001300942.2(EMSY):​c.1559-4G>A variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.00001893
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.329
• Publications: 28 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMSY	NM_001300942.2	MANE Select	c.1559-4G>A		splice_region intron	N/A	NP_001287871.1
	EMSY	NM_001300943.2		c.1517-4G>A		splice_region intron	N/A	NP_001287872.1
	EMSY	NM_001300944.2		c.1559-4G>A		splice_region intron	N/A	NP_001287873.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMSY	ENST00000695367.1	MANE Select	c.1559-4G>A		splice_region intron	N/A	ENSP00000511840.1
	EMSY	ENST00000524767.5	TSL:1	c.1559-4G>A		splice_region intron	N/A	ENSP00000433205.1
	EMSY	ENST00000525038.5	TSL:1	c.1559-4G>A		splice_region intron	N/A	ENSP00000436968.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87968 AN: 151782 Hom.: 26411 Cov.: 31

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

GnomAD2 exomes AF: 0.650 AC: 159672 AN: 245470 AF XY: 0.653

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 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.: 38 AF XY: 0.626 AC XY: 452430 AN XY: 723072

African (AFR) AF: 0.421 AC: 13958 AN: 33154

American (AMR) AF: 0.770 AC: 33345 AN: 43326

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 13791 AN: 25800

East Asian (EAS) AF: 0.814 AC: 32235 AN: 39592

South Asian (SAS) AF: 0.719 AC: 60989 AN: 84834

European-Finnish (FIN) AF: 0.638 AC: 34027 AN: 53324

Middle Eastern (MID) AF: 0.586 AC: 3349 AN: 5716

European-Non Finnish (NFE) AF: 0.611 AC: 677179 AN: 1108110

Other (OTH) AF: 0.616 AC: 36948 AN: 60014

GnomAD4 genome AF: 0.580 AC: 88037 AN: 151902 Hom.: 26440 Cov.: 31 AF XY: 0.585 AC XY: 43421 AN XY: 74214

African (AFR) AF: 0.430 AC: 17824 AN: 41408

American (AMR) AF: 0.681 AC: 10390 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1880 AN: 3468

East Asian (EAS) AF: 0.820 AC: 4240 AN: 5170

South Asian (SAS) AF: 0.733 AC: 3527 AN: 4812

European-Finnish (FIN) AF: 0.632 AC: 6662 AN: 10534

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41665 AN: 67946

Other (OTH) AF: 0.577 AC: 1217 AN: 2108

Alfa AF: 0.599 Hom.: 94537

Bravo AF: 0.575

Asia WGS AF: 0.746 AC: 2592 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EMSY-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.94
DANN	Benign	0.50
PhyloP100		0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2508740; hg19: chr11-76227182;