rs2788

Variant names:

• chr15-43772688-A-G
• rs2788
• ENST00000417761.2:n.*1926T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000417761.2(ENSG00000262560):​n.*1926T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 154,008 control chromosomes in the GnomAD database, including 2,622 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 0.16 (2614 hom., cov: 33)
  • Exomes 𝑓: 0.092 (8 hom.)
• Consequence: ENSG00000262560 ENST00000417761.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 14 publications found

Genes affected

ENSG00000262560 (HGNC:):

PDIA3 (HGNC:4606): (protein disulfide isomerase family A member 3) This gene encodes a protein of the endoplasmic reticulum that interacts with lectin chaperones calreticulin and calnexin to modulate folding of newly synthesized glycoproteins. The protein was once thought to be a phospholipase; however, it has been demonstrated that the protein actually has protein disulfide isomerase activity. It is thought that complexes of lectins and this protein mediate protein folding by promoting formation of disulfide bonds in their glycoprotein substrates. This protein also functions as a molecular chaperone that prevents the formation of protein aggregates. [provided by RefSeq, Dec 2016]

ELL3 (HGNC:23113): (elongation factor for RNA polymerase II 3) Predicted to enable cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription, DNA-templated and transcription by RNA polymerase II. Located in several cellular components, including chromosome; cytosol; and nuclear lumen. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000417761.2. 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
	PDIA3	NM_005313.5	MANE Select	c.*1470A>G		3_prime_UTR	Exon 13 of 13	NP_005304.3
	ELL3	NM_025165.3	MANE Select	c.*428T>C		3_prime_UTR	Exon 11 of 11	NP_079441.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000262560	ENST00000417761.2	TSL:2	n.*1926T>C		non_coding_transcript_exon	Exon 17 of 17	ENSP00000415219.2
	PDIA3	ENST00000300289.10	TSL:1 MANE Select	c.*1470A>G		3_prime_UTR	Exon 13 of 13	ENSP00000300289.5
	ELL3	ENST00000319359.8	TSL:1 MANE Select	c.*428T>C		3_prime_UTR	Exon 11 of 11	ENSP00000320346.3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24563 AN: 152170 Hom.: 2606 Cov.: 33

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.0924 AC: 159 AN: 1720 Hom.: 8 Cov.: 0 AF XY: 0.0935 AC XY: 89 AN XY: 952

African (AFR) AF: 0.265 AC: 18 AN: 68

American (AMR) AF: 0.188 AC: 9 AN: 48

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 9 AN: 56

East Asian (EAS) AF: 0.295 AC: 13 AN: 44

South Asian (SAS) AF: 0.0714 AC: 2 AN: 28

European-Finnish (FIN) AF: 0.0221 AC: 3 AN: 136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0743 AC: 91 AN: 1224

Other (OTH) AF: 0.123 AC: 14 AN: 114

GnomAD4 genome AF: 0.162 AC: 24613 AN: 152288 Hom.: 2614 Cov.: 33 AF XY: 0.160 AC XY: 11897 AN XY: 74478

African (AFR) AF: 0.290 AC: 12035 AN: 41544

American (AMR) AF: 0.178 AC: 2725 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1422 AN: 5188

South Asian (SAS) AF: 0.142 AC: 687 AN: 4830

European-Finnish (FIN) AF: 0.0405 AC: 430 AN: 10616

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0916 AC: 6233 AN: 68026

Other (OTH) AF: 0.155 AC: 327 AN: 2112

Alfa AF: 0.124 Hom.: 1911

Bravo AF: 0.181

Asia WGS AF: 0.207 AC: 718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.70
PhyloP100		1.4
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: rs2788; hg19: chr15-44064886;