rs8192884

Variant names:

• chr13-46790924-G-A
• rs8192884
• NM_001984.2:c.68+422C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001984.2. 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
	ESD	NM_001984.2	MANE Select	c.68+422C>T		intron	N/A	NP_001975.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESD	ENST00000378720.8	TSL:1 MANE Select	c.68+422C>T		intron	N/A	ENSP00000367992.3
	ESD	ENST00000471867.3	TSL:2	c.68+422C>T		intron	N/A	ENSP00000476193.2
	ESD	ENST00000378697.5	TSL:5	c.-84-263C>T		intron	N/A	ENSP00000367969.1

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

African (AFR) AF: 0.0792 AC: 3286 AN: 41474

American (AMR) AF: 0.133 AC: 2036 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2054 AN: 5164

South Asian (SAS) AF: 0.237 AC: 1139 AN: 4810

European-Finnish (FIN) AF: 0.0862 AC: 913 AN: 10592

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0976 AC: 6632 AN: 67972

Other (OTH) AF: 0.141 AC: 298 AN: 2116

Alfa AF: 0.113 Hom.: 758

Bravo AF: 0.114

Asia WGS AF: 0.270 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.76
PhyloP100		-1.0
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: rs8192884; hg19: chr13-47365059;