chr11-76516138-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001300942.2(EMSY):​c.1559-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000825 in 1,455,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: EMSY NM_001300942.2 splice_region, intron
• Scores: Splicing: ADA: 0.00001559
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

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>T		splice_region intron	N/A	NP_001287871.1	Q7Z589-7
	EMSY	NM_001300943.2		c.1517-4G>T		splice_region intron	N/A	NP_001287872.1	Q7Z589-5
	EMSY	NM_001300944.2		c.1559-4G>T		splice_region intron	N/A	NP_001287873.1	Q7Z589-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMSY	ENST00000695367.1	MANE Select	c.1559-4G>T		splice_region intron	N/A	ENSP00000511840.1	Q7Z589-7
	EMSY	ENST00000524767.5	TSL:1	c.1559-4G>T		splice_region intron	N/A	ENSP00000433205.1	Q7Z589-7
	EMSY	ENST00000525038.5	TSL:1	c.1559-4G>T		splice_region intron	N/A	ENSP00000436968.1	Q7Z589-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000122 AC: 3 AN: 245470 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000825 AC: 12 AN: 1455152 Hom.: 0 Cov.: 38 AF XY: 0.00000967 AC XY: 7 AN XY: 723686

African (AFR) AF: 0.00 AC: 0 AN: 33186

American (AMR) AF: 0.00 AC: 0 AN: 43352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25814

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 84944

European-Finnish (FIN) AF: 0.000225 AC: 12 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109118

Other (OTH) AF: 0.00 AC: 0 AN: 60074

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 94537

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.66
DANN	Benign	0.54
PhyloP100		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
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;