rs11600501

Variant names:

• chr11-76523141-C-T
• rs11600501
• NM_001300942.2:c.1730-14C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• Publications: 9 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 -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.

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.1730-14C>T		intron	N/A	NP_001287871.1
	EMSY	NM_001300943.2		c.1688-14C>T		intron	N/A	NP_001287872.1
	EMSY	NM_001300944.2		c.1730-14C>T		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.1730-14C>T		intron	N/A	ENSP00000511840.1
	EMSY	ENST00000524767.5	TSL:1	c.1730-14C>T		intron	N/A	ENSP00000433205.1
	EMSY	ENST00000525038.5	TSL:1	c.1730-14C>T		intron	N/A	ENSP00000436968.1

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

GnomAD2 exomes AF: 0.0342 AC: 8161 AN: 238458 AF XY: 0.0342

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

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: 6 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

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

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: 0 AN: 5186

South Asian (SAS) AF: 0.0166 AC: 80 AN: 4828

European-Finnish (FIN) AF: 0.0120 AC: 127 AN: 10608

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0452 AC: 3073 AN: 68022

Other (OTH) AF: 0.0464 AC: 98 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.80
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11600501; hg19: chr11-76234185;