rs2794658

Variant names:

• chr13-46776347-G-A
• rs2794658
• NM_001984.2:c.768+1109C>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.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
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESD	NM_001984.2	MANE Select	c.768+1109C>T		intron	N/A	NP_001975.1	P10768

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESD	ENST00000378720.8	TSL:1 MANE Select	c.768+1109C>T		intron	N/A	ENSP00000367992.3	P10768
	ESD	ENST00000471867.3	TSL:2	c.*1088C>T		3_prime_UTR	Exon 9 of 9	ENSP00000476193.2	U3KQT1
	ESD	ENST00000898802.1		c.783+1109C>T		intron	N/A	ENSP00000568861.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.396 AC: 16429 AN: 41456

American (AMR) AF: 0.178 AC: 2716 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 397 AN: 3462

East Asian (EAS) AF: 0.399 AC: 2064 AN: 5170

South Asian (SAS) AF: 0.336 AC: 1618 AN: 4822

European-Finnish (FIN) AF: 0.0583 AC: 618 AN: 10592

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.104 AC: 7090 AN: 67950

Other (OTH) AF: 0.218 AC: 459 AN: 2110

Alfa AF: 0.139 Hom.: 1543

Bravo AF: 0.223

Asia WGS AF: 0.334 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.73
PhyloP100		-0.036
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: rs2794658; hg19: chr13-47350482;