rs1418267

Positions:

• chr9-100044292-A-G
• chr9-100044292-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.286+8125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,092 control chromosomes in the GnomAD database, including 37,215 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 0.69 (37215 hom., cov: 32)
• Consequence: ERP44 NM_015051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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]

LOC105376176 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• 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.286+8125T>C		intron_variant		ENST00000262455.7
LOC105376176	XR_001746547.2	n.18437A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERP44	ENST00000262455.7	c.286+8125T>C		intron_variant		1	NM_015051.3	P1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104510 AN: 151974 Hom.: 37163 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.688 AC: 104623 AN: 152092 Hom.: 37215 Cov.: 32 AF XY: 0.692 AC XY: 51448 AN XY: 74336

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.667

Alfa AF: 0.625 Hom.: 3606

Bravo AF: 0.704

Asia WGS AF: 0.819 AC: 2843 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.2
DANN	Benign	0.47

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: rs1418267; hg19: chr9-102806574;