11-76451851-C-T

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.71-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,544,916 control chromosomes in the GnomAD database, including 57 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 0.00091 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (53 hom.)
• Consequence: EMSY NM_001300942.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003057
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0840

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=-0.36).
• BP6: Variant 11-76451851-C-T is Benign according to our data. Variant chr11-76451851-C-T is described in ClinVar as [Benign]. Clinvar id is 726525.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000913 (139/152172) while in subpopulation SAS AF= 0.0275 (133/4828). AF 95% confidence interval is 0.0237. There are 4 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 140 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMSY	NM_001300942.2	c.71-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000695367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMSY	ENST00000695367.1	c.71-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001300942.2

Frequencies

GnomAD3 genomes AF: 0.000921 AC: 140 AN: 152054 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0277

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00351 AC: 709 AN: 202202 Hom.: 13 AF XY: 0.00456 AC XY: 506 AN XY: 110976

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000144

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000745

Gnomad SAS exome AF: 0.0314

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000304

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00168 AC: 2342 AN: 1392744 Hom.: 53 Cov.: 27 AF XY: 0.00238 AC XY: 1646 AN XY: 692450

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000129

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0299

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000148

Gnomad4 OTH exome AF: 0.00193

GnomAD4 genome AF: 0.000913 AC: 139 AN: 152172 Hom.: 4 Cov.: 32 AF XY: 0.00144 AC XY: 107 AN XY: 74392

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0275

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000385 Hom.: 2

Bravo AF: 0.000234

Asia WGS AF: 0.0170 AC: 59 AN: 3476

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

Jun 25, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	12
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00031
dbscSNV1_RF	Benign	0.024
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: rs529427104; hg19: chr11-76162895;