18-21540013-G-GAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_052911.3(ESCO1):c.1954-5_1954-4insAT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (8 hom., cov: 0)
  • Exomes 𝑓: 0.0036 (0 hom.)
• Consequence: ESCO1 NM_052911.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.640

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 -10 ACMG points.

• BP6: Variant 18-21540013-G-GAT is Benign according to our data. Variant chr18-21540013-G-GAT is described in ClinVar as [Benign]. Clinvar id is 716495.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00642 (952/148274) while in subpopulation AFR AF= 0.0188 (758/40378). AF 95% confidence interval is 0.0177. There are 8 homozygotes in gnomad4. There are 457 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd at 947 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESCO1	NM_052911.3	c.1954-5_1954-4insAT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000269214.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESCO1	ENST00000269214.10	c.1954-5_1954-4insAT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_052911.3	P1
ESCO1	ENST00000622333.1	c.-51-5_-51-4insAT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2
ESCO1	ENST00000383276.1	c.2078-5_2078-4insAT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00639 AC: 947 AN: 148182 Hom.: 8 Cov.: 0

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00238

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000394

Gnomad SAS AF: 0.00321

Gnomad FIN AF: 0.000510

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.00791

GnomAD3 exomes AF: 0.00319 AC: 426 AN: 133396 Hom.: 0 AF XY: 0.00311 AC XY: 227 AN XY: 73092

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.00328

Gnomad ASJ exome AF: 0.00128

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00427

Gnomad FIN exome AF: 0.000842

Gnomad NFE exome AF: 0.00228

Gnomad OTH exome AF: 0.00521

GnomAD4 exome AF: 0.00360 AC: 3976 AN: 1104026 Hom.: 0 Cov.: 0 AF XY: 0.00351 AC XY: 1952 AN XY: 556168

Gnomad4 AFR exome AF: 0.0163

Gnomad4 AMR exome AF: 0.00248

Gnomad4 ASJ exome AF: 0.00114

Gnomad4 EAS exome AF: 0.0000316

Gnomad4 SAS exome AF: 0.00355

Gnomad4 FIN exome AF: 0.000756

Gnomad4 NFE exome AF: 0.00362

Gnomad4 OTH exome AF: 0.00384

GnomAD4 genome AF: 0.00642 AC: 952 AN: 148274 Hom.: 8 Cov.: 0 AF XY: 0.00633 AC XY: 457 AN XY: 72154

Gnomad4 AFR AF: 0.0188

Gnomad4 AMR AF: 0.00237

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000395

Gnomad4 SAS AF: 0.00322

Gnomad4 FIN AF: 0.000510

Gnomad4 NFE AF: 0.00181

Gnomad4 OTH AF: 0.00783

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

Apr 19, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35031202; hg19: chr18-19119974;