rs4245443

Positions:

• chr11-76472880-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001300942.2(EMSY):​c.1153+40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,597,998 control chromosomes in the GnomAD database, including 290,803 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 0.55 (24111 hom., cov: 32)
  • Exomes 𝑓: 0.60 (266692 hom.)
• Consequence: EMSY NM_001300942.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.70

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMSY	NM_001300942.2	c.1153+40A>G		intron_variant		ENST00000695367.1	NP_001287871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMSY	ENST00000695367.1	c.1153+40A>G		intron_variant			NM_001300942.2	ENSP00000511840.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83717 AN: 151956 Hom.: 24089 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.547

GnomAD3 exomes AF: 0.622 AC: 153097 AN: 246050 Hom.: 49101 AF XY: 0.624 AC XY: 82904 AN XY: 132912

Gnomad AFR exome AF: 0.378

Gnomad AMR exome AF: 0.775

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.722

Gnomad SAS exome AF: 0.675

Gnomad FIN exome AF: 0.613

Gnomad NFE exome AF: 0.599

Gnomad OTH exome AF: 0.601

GnomAD4 exome AF: 0.604 AC: 872928 AN: 1445924 Hom.: 266692 Cov.: 31 AF XY: 0.606 AC XY: 434309 AN XY: 717262

Gnomad4 AFR exome AF: 0.375

Gnomad4 AMR exome AF: 0.763

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.717

Gnomad4 SAS exome AF: 0.672

Gnomad4 FIN exome AF: 0.613

Gnomad4 NFE exome AF: 0.599

Gnomad4 OTH exome AF: 0.586

GnomAD4 genome AF: 0.551 AC: 83778 AN: 152074 Hom.: 24111 Cov.: 32 AF XY: 0.555 AC XY: 41259 AN XY: 74324

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.546

Alfa AF: 0.593 Hom.: 36837

Bravo AF: 0.548

Asia WGS AF: 0.643 AC: 2234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.034
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4245443; hg19: chr11-76183924; COSMIC: COSV58257793;