rs1749569

Positions:

• chr1-236256281-T-G

Variant summary

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

The NM_019891.4(ERO1B):​c.223-2776A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,976 control chromosomes in the GnomAD database, including 4,815 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 0.25 (4815 hom., cov: 32)
• Consequence: ERO1B NM_019891.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

Genes affected

ERO1B (HGNC:14355): (endoplasmic reticulum oxidoreductase 1 beta) Enables thiol oxidase activity. Involved in protein folding in endoplasmic reticulum. Predicted to be located in membrane. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ERO1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERO1B	NM_019891.4	c.223-2776A>C		intron_variant		ENST00000354619.10	NP_063944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERO1B	ENST00000354619.10	c.223-2776A>C		intron_variant		1	NM_019891.4	ENSP00000346635.5

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37586 AN: 151858 Hom.: 4805 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.248 AC: 37633 AN: 151976 Hom.: 4815 Cov.: 32 AF XY: 0.251 AC XY: 18668 AN XY: 74298

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.254

Alfa AF: 0.247 Hom.: 561

Bravo AF: 0.245

Asia WGS AF: 0.279 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.52

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: rs1749569; hg19: chr1-236419581;