11-76463865-C-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BS1 BS2

The NM_001300942.2(EMSY):c.661C>A(p.Arg221=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00259 in 1,614,096 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (29 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (32 hom.)
• Consequence: EMSY NM_001300942.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.87

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BP6: Variant 11-76463865-C-A is Benign according to our data. Variant chr11-76463865-C-A is described in ClinVar as [Benign]. Clinvar id is 786204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1864/152216) while in subpopulation AFR AF= 0.0407 (1691/41526). AF 95% confidence interval is 0.0391. There are 29 homozygotes in gnomad4. There are 856 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1861 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMSY	NM_001300942.2	c.661C>A	p.Arg221=	synonymous_variant	8/22	ENST00000695367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMSY	ENST00000695367.1	c.661C>A	p.Arg221=	synonymous_variant	8/22		NM_001300942.2

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1861 AN: 152098 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00485

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00373 AC: 939 AN: 251464 Hom.: 10 AF XY: 0.00285 AC XY: 388 AN XY: 135904

Gnomad AFR exome AF: 0.0415

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00159 AC: 2321 AN: 1461880 Hom.: 32 Cov.: 31 AF XY: 0.00137 AC XY: 995 AN XY: 727242

Gnomad4 AFR exome AF: 0.0407

Gnomad4 AMR exome AF: 0.00282

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000228

Gnomad4 OTH exome AF: 0.00394

GnomAD4 genome AF: 0.0122 AC: 1864 AN: 152216 Hom.: 29 Cov.: 32 AF XY: 0.0115 AC XY: 856 AN XY: 74426

Gnomad4 AFR AF: 0.0407

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00692 Hom.: 7

Bravo AF: 0.0138

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
Cadd	Benign	12
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs61741528; hg19: chr11-76174909;