rs1529192

Positions:

• chr9-100083781-A-G
• chr9-100083781-A-T

Variant summary

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

The NM_015051.3(ERP44):​c.57+15003T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,072 control chromosomes in the GnomAD database, including 36,073 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 0.68 (36073 hom., cov: 32)
• Consequence: ERP44 NM_015051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

Genes affected

ERP44 (HGNC:18311): (endoplasmic reticulum protein 44) This gene encodes a member of the protein disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins. It has an inferred N-terminal signal peptide, a catalytically active thioredoxin (TRX) domain, two TRX-like domains and a C-terminal ER-retention sequence. This protein functions as a pH-regulated chaperone of the secretory pathway and likely plays a role in protein quality control at the endoplasmic reticulum - Golgi interface. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERP44	NM_015051.3	c.57+15003T>C		intron_variant		ENST00000262455.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERP44	ENST00000262455.7	c.57+15003T>C		intron_variant		1	NM_015051.3	P1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102840 AN: 151954 Hom.: 36023 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.677 AC: 102951 AN: 152072 Hom.: 36073 Cov.: 32 AF XY: 0.681 AC XY: 50635 AN XY: 74316

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.658

Alfa AF: 0.638 Hom.: 6036

Bravo AF: 0.692

Asia WGS AF: 0.816 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.7
DANN	Benign	0.42

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: rs1529192; hg19: chr9-102846063;