18-21535170-T-C

Variant names:

• chr18-21535170-T-C
• rs16942790
• NM_052911.3:c.2187+872A>G

Variant summary

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

The NM_052911.3(ESCO1):​c.2187+872A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,998 control chromosomes in the GnomAD database, including 10,594 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 0.32 (10594 hom., cov: 31)
• Consequence: ESCO1 NM_052911.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.783
• Publications: 5 publications found

Genes affected

ESCO1 (HGNC:24645): (establishment of sister chromatid cohesion N-acetyltransferase 1) Enables identical protein binding activity; peptide-lysine-N-acetyltransferase activity; and zinc ion binding activity. Involved in peptidyl-lysine acetylation; post-translational protein acetylation; and regulation of DNA replication. Located in chromatin. [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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052911.3. 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
	ESCO1	NM_052911.3	MANE Select	c.2187+872A>G		intron	N/A	NP_443143.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESCO1	ENST00000269214.10	TSL:1 MANE Select	c.2187+872A>G		intron	N/A	ENSP00000269214.4
	ESCO1	ENST00000622333.1	TSL:2	c.183+872A>G		intron	N/A	ENSP00000484873.1
	ESCO1	ENST00000383276.2	TSL:2	n.*205+872A>G		intron	N/A	ENSP00000372763.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48353 AN: 151880 Hom.: 10571 Cov.: 31

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.319 AC: 48426 AN: 151998 Hom.: 10594 Cov.: 31 AF XY: 0.323 AC XY: 23963 AN XY: 74296

African (AFR) AF: 0.586 AC: 24280 AN: 41422

American (AMR) AF: 0.407 AC: 6223 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2286 AN: 5160

South Asian (SAS) AF: 0.340 AC: 1639 AN: 4816

European-Finnish (FIN) AF: 0.162 AC: 1715 AN: 10558

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10806 AN: 67992

Other (OTH) AF: 0.303 AC: 637 AN: 2100

Alfa AF: 0.231 Hom.: 15503

Bravo AF: 0.348

Asia WGS AF: 0.467 AC: 1622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.0
DANN	Benign	0.85
PhyloP100		0.78
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: rs16942790; hg19: chr18-19115131;