chr11-76470587-G-A

Variant names:

• chr11-76470587-G-A
• rs10899221
• NM_001300942.2:c.877-1977G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001300942.2(EMSY):​c.877-1977G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 151,938 control chromosomes in the GnomAD database, including 345 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 0.056 (345 hom., cov: 32)
• Consequence: EMSY NM_001300942.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300942.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMSY	NM_001300942.2	MANE Select	c.877-1977G>A		intron	N/A	NP_001287871.1
	EMSY	NM_001300943.2		c.835-1977G>A		intron	N/A	NP_001287872.1
	EMSY	NM_001300944.2		c.877-1977G>A		intron	N/A	NP_001287873.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMSY	ENST00000695367.1	MANE Select	c.877-1977G>A		intron	N/A	ENSP00000511840.1
	EMSY	ENST00000524767.5	TSL:1	c.877-1977G>A		intron	N/A	ENSP00000433205.1
	EMSY	ENST00000525038.5	TSL:1	c.877-1977G>A		intron	N/A	ENSP00000436968.1

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8579 AN: 151818 Hom.: 344 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0915

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.0436

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0565 AC: 8581 AN: 151938 Hom.: 345 Cov.: 32 AF XY: 0.0595 AC XY: 4419 AN XY: 74246

African (AFR) AF: 0.0137 AC: 568 AN: 41468

American (AMR) AF: 0.0333 AC: 508 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 153 AN: 3468

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5166

South Asian (SAS) AF: 0.0919 AC: 443 AN: 4818

European-Finnish (FIN) AF: 0.124 AC: 1296 AN: 10486

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0809 AC: 5498 AN: 67952

Other (OTH) AF: 0.0436 AC: 92 AN: 2110

Alfa AF: 0.0705 Hom.: 942

Bravo AF: 0.0466

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.36
PhyloP100		0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10899221; hg19: chr11-76181631;