rs7028939

Positions:

• chr9-100046403-A-G

Variant summary

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

The ENST00000262455.7(ERP44):​c.286+6014T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,094 control chromosomes in the GnomAD database, including 4,254 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 0.19 (4254 hom., cov: 32)
• Consequence: ERP44 ENST00000262455.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERP44	NM_015051.3	c.286+6014T>C		intron_variant		ENST00000262455.7	NP_055866.1
LOC105376176	XR_001746547.2	n.20548A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERP44	ENST00000262455.7	c.286+6014T>C		intron_variant		1	NM_015051.3	ENSP00000262455	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28552 AN: 151976 Hom.: 4246 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0478

Gnomad EAS AF: 0.00326

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.188 AC: 28577 AN: 152094 Hom.: 4254 Cov.: 32 AF XY: 0.184 AC XY: 13656 AN XY: 74350

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0478

Gnomad4 EAS AF: 0.00327

Gnomad4 SAS AF: 0.0402

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.144

Alfa AF: 0.121 Hom.: 786

Bravo AF: 0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.79
DANN	Benign	0.88

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: rs7028939; hg19: chr9-102808685;