rs16942790

Positions:

• chr18-21535170-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESCO1	NM_052911.3	c.2187+872A>G		intron_variant		ENST00000269214.10
ESCO1	XM_011525798.2	c.2187+872A>G		intron_variant
ESCO1	XM_011525799.4	c.2097+872A>G		intron_variant
ESCO1	XM_047437285.1	c.2097+872A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESCO1	ENST00000269214.10	c.2187+872A>G		intron_variant		1	NM_052911.3	P1
ESCO1	ENST00000622333.1	c.183+872A>G		intron_variant		2
ESCO1	ENST00000383276.1	c.*205+872A>G		intron_variant, NMD_transcript_variant		2

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

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.303

Alfa AF: 0.203 Hom.: 6965

Bravo AF: 0.348

Asia WGS AF: 0.467 AC: 1622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.0
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs16942790; hg19: chr18-19115131;