rs2794658

Positions:

• chr13-46776347-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.768+1109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,034 control chromosomes in the GnomAD database, including 4,674 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 0.21 (4674 hom., cov: 32)
  • Exomes 𝑓: 0.050 (0 hom.)
• Consequence: ESD NM_001984.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESD	NM_001984.2	c.768+1109C>T		intron_variant		ENST00000378720.8	NP_001975.1
ESD	XM_005266278.4	c.768+1109C>T		intron_variant			XP_005266335.1
ESD	XM_011534954.2	c.768+1109C>T		intron_variant			XP_011533256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESD	ENST00000378720.8	c.768+1109C>T		intron_variant		1	NM_001984.2	ENSP00000367992.3
ESD	ENST00000471867	c.*1088C>T		3_prime_UTR_variant	9/9	2		ENSP00000476193.2
ESD	ENST00000378697.5	c.681+1109C>T		intron_variant		5		ENSP00000367969.1
ESD	ENST00000412582.5	c.610-655C>T		intron_variant		3		ENSP00000391350.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31504 AN: 151894 Hom.: 4656 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.0500 AC: 1 AN: 20 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 SAS exome AF: 0.250

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.208 AC: 31578 AN: 152014 Hom.: 4674 Cov.: 32 AF XY: 0.208 AC XY: 15428 AN XY: 74336

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.0583

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.218

Alfa AF: 0.138 Hom.: 1128

Bravo AF: 0.223

Asia WGS AF: 0.334 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.73

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: rs2794658; hg19: chr13-47350482;