rs11600501

Positions:

• chr11-76523141-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001300942.2(EMSY):​c.1730-14C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 6035 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMSY	NM_001300942.2	c.1730-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000695367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMSY	ENST00000695367.1	c.1730-14C>T		splice_polypyrimidine_tract_variant, intron_variant			NM_001300942.2

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6018 AN: 152108 Hom.: 142 Cov.: 32

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

GnomAD3 exomes AF: 0.0342 AC: 8161 AN: 238458 Hom.: 181 AF XY: 0.0342 AC XY: 4410 AN XY: 129046

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 SAS exome AF: 0.0182

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.: 30 AF XY: 0.0397 AC XY: 28568 AN XY: 720212

Gnomad4 AFR exome AF: 0.0450

Gnomad4 AMR exome AF: 0.0333

Gnomad4 ASJ exome AF: 0.0364

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0192

Gnomad4 FIN exome AF: 0.0174

Gnomad4 NFE exome AF: 0.0445

Gnomad4 OTH exome AF: 0.0401

GnomAD4 genome AF: 0.0396 AC: 6035 AN: 152226 Hom.: 143 Cov.: 32 AF XY: 0.0383 AC XY: 2854 AN XY: 74430

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.0510

Gnomad4 ASJ AF: 0.0326

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0452

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0405 Hom.: 40

Bravo AF: 0.0420

Asia WGS AF: 0.0110 AC: 38 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	15
DANN	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs11600501; hg19: chr11-76234185;