chr18-21554414-A-T

Variant names:

• chr18-21554414-A-T
• rs4800795
• NM_052911.3:c.1953+6445T>A

Variant summary

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

The NM_052911.3(ESCO1):​c.1953+6445T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,072 control chromosomes in the GnomAD database, including 21,557 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 0.50 (21557 hom., cov: 32)
• Consequence: ESCO1 NM_052911.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 3 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESCO1	NM_052911.3	MANE Select	c.1953+6445T>A		intron	N/A	NP_443143.2	Q5FWF5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESCO1	ENST00000269214.10	TSL:1 MANE Select	c.1953+6445T>A		intron	N/A	ENSP00000269214.4	Q5FWF5-1
	ESCO1	ENST00000892205.1		c.1953+6445T>A		intron	N/A	ENSP00000562264.1
	ESCO1	ENST00000923542.1		c.1953+6445T>A		intron	N/A	ENSP00000593601.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75682 AN: 151952 Hom.: 21512 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.498 AC: 75788 AN: 152072 Hom.: 21557 Cov.: 32 AF XY: 0.501 AC XY: 37241 AN XY: 74330

African (AFR) AF: 0.781 AC: 32403 AN: 41478

American (AMR) AF: 0.529 AC: 8079 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2420 AN: 5164

South Asian (SAS) AF: 0.506 AC: 2441 AN: 4824

European-Finnish (FIN) AF: 0.376 AC: 3978 AN: 10576

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23784 AN: 67970

Other (OTH) AF: 0.484 AC: 1020 AN: 2108

Alfa AF: 0.231 Hom.: 454

Bravo AF: 0.521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.94
DANN	Benign	0.27
PhyloP100		-0.49
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: rs4800795; hg19: chr18-19134375;