11-76523148-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001300942.2(EMSY):c.1730-7T>C 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 0.00172 in 1,603,380 control chromosomes in the GnomAD database, including 47 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 0.0016 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (44 hom.)
• Consequence: EMSY NM_001300942.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0002017
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.418

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 11-76523148-T-C is Benign according to our data. Variant chr11-76523148-T-C is described in ClinVar as [Benign]. Clinvar id is 781965.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 245 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMSY	NM_001300942.2	c.1730-7T>C		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.1730-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001300942.2

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 245 AN: 152196 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00291 AC: 698 AN: 240270 Hom.: 17 AF XY: 0.00292 AC XY: 379 AN XY: 129848

Gnomad AFR exome AF: 0.000249

Gnomad AMR exome AF: 0.000190

Gnomad ASJ exome AF: 0.0570

Gnomad EAS exome AF: 0.0000561

Gnomad SAS exome AF: 0.000145

Gnomad FIN exome AF: 0.0000468

Gnomad NFE exome AF: 0.00117

Gnomad OTH exome AF: 0.00291

GnomAD4 exome AF: 0.00173 AC: 2515 AN: 1451066 Hom.: 44 Cov.: 30 AF XY: 0.00178 AC XY: 1283 AN XY: 721794

Gnomad4 AFR exome AF: 0.000122

Gnomad4 AMR exome AF: 0.000239

Gnomad4 ASJ exome AF: 0.0535

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000143

Gnomad4 FIN exome AF: 0.0000564

Gnomad4 NFE exome AF: 0.000775

Gnomad4 OTH exome AF: 0.00371

GnomAD4 genome AF: 0.00161 AC: 245 AN: 152314 Hom.: 3 Cov.: 33 AF XY: 0.00168 AC XY: 125 AN XY: 74476

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00495 Hom.: 9

Bravo AF: 0.00183

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

Feb 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	11
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00020
dbscSNV1_RF	Benign	0.11
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: rs199909771; hg19: chr11-76234192;