11-76451964-T-C

Position:

• chr11-76451964-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001300942.2(EMSY):​c.170+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00093 in 1,531,718 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (7 hom.)
• Consequence: EMSY NM_001300942.2 splice_region, intron
• Scores: Splicing: ADA: 0.0007935
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.74

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 11-76451964-T-C is Benign according to our data. Variant chr11-76451964-T-C is described in ClinVar as [Benign]. Clinvar id is 786203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00498 (759/152296) while in subpopulation AFR AF= 0.0173 (721/41564). AF 95% confidence interval is 0.0163. There are 4 homozygotes in gnomad4. There are 361 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 759 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMSY	NM_001300942.2	c.170+7T>C		splice_region_variant, intron_variant		ENST00000695367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMSY	ENST00000695367.1	c.170+7T>C		splice_region_variant, intron_variant			NM_001300942.2

Frequencies

GnomAD3 genomes AF: 0.00501 AC: 763 AN: 152178 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.00139 AC: 279 AN: 200612 Hom.: 4 AF XY: 0.00101 AC XY: 111 AN XY: 109902

Gnomad AFR exome AF: 0.0193

Gnomad AMR exome AF: 0.000591

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000449

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000716

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.000482 AC: 665 AN: 1379422 Hom.: 7 Cov.: 23 AF XY: 0.000419 AC XY: 288 AN XY: 687428

Gnomad4 AFR exome AF: 0.0181

Gnomad4 AMR exome AF: 0.000785

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000528

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.0000225

Gnomad4 OTH exome AF: 0.00138

GnomAD4 genome AF: 0.00498 AC: 759 AN: 152296 Hom.: 4 Cov.: 32 AF XY: 0.00485 AC XY: 361 AN XY: 74472

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00256 Hom.: 0

Bravo AF: 0.00586

Asia WGS AF: 0.000866 AC: 4 AN: 3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00079
dbscSNV1_RF	Benign	0.030
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: rs73493461; hg19: chr11-76163008;