rs8192884

chr13-46790924-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001984.2(ESD):c.68+422C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,090 control chromosomes in the GnomAD database, including 1,255 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 0.11 (1255 hom., cov: 32)
• Consequence: ESD NM_001984.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

ESD (HGNC:3465): (esterase D) This gene encodes a serine hydrolase that belongs to the esterase D family. The encoded enzyme is active toward numerous substrates including O-acetylated sialic acids, and it may be involved in the recycling of sialic acids. This gene is used as a genetic marker for retinoblastoma and Wilson's disease. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESD	NM_001984.2	c.68+422C>T		intron_variant		ENST00000378720.8
ESD	XM_005266278.4	c.68+422C>T		intron_variant
ESD	XM_011534954.2	c.68+422C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESD	ENST00000378720.8	c.68+422C>T		intron_variant		1	NM_001984.2	P1
ESD	ENST00000378697.5	c.-84-263C>T		intron_variant		5
ESD	ENST00000471867.3	c.68+422C>T		intron_variant		2
ESD	ENST00000495654.1	n.117+422C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16923 AN: 151972 Hom.: 1255 Cov.: 32

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.0862

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0976

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.111 AC: 16942 AN: 152090 Hom.: 1255 Cov.: 32 AF XY: 0.114 AC XY: 8481 AN XY: 74366

Gnomad4 AFR AF: 0.0792

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.0862

Gnomad4 NFE AF: 0.0976

Gnomad4 OTH AF: 0.141

Alfa AF: 0.106 Hom.: 416

Bravo AF: 0.114

Asia WGS AF: 0.270 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.58
Dann	Benign	0.76

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: rs8192884; hg19: chr13-47365059;