rs1726654

Variant names:

• chr1-236254423-A-G
• rs1726654
• NM_019891.4:c.223-918T>C

Variant summary

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

The NM_019891.4(ERO1B):​c.223-918T>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 151,938 control chromosomes in the GnomAD database, including 4,858 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 (4858 hom., cov: 31)
• Consequence: ERO1B NM_019891.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 3 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• 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 rank	MANE	Protein	UniProt
ERO1B	NM_019891.4	c.223-918T>C		intron_variant	Intron 2 of 15	ENST00000354619.10	NP_063944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERO1B	ENST00000354619.10	c.223-918T>C		intron_variant	Intron 2 of 15	1	NM_019891.4	ENSP00000346635.5

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37631 AN: 151820 Hom.: 4848 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.248 AC: 37678 AN: 151938 Hom.: 4858 Cov.: 31 AF XY: 0.252 AC XY: 18676 AN XY: 74246

African (AFR) AF: 0.200 AC: 8279 AN: 41430

American (AMR) AF: 0.283 AC: 4324 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3470

East Asian (EAS) AF: 0.381 AC: 1958 AN: 5142

South Asian (SAS) AF: 0.198 AC: 955 AN: 4812

European-Finnish (FIN) AF: 0.361 AC: 3798 AN: 10518

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.248 AC: 16889 AN: 67978

Other (OTH) AF: 0.256 AC: 540 AN: 2110

Alfa AF: 0.247 Hom.: 562

Bravo AF: 0.245

Asia WGS AF: 0.279 AC: 969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.78
PhyloP100		-0.15
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: rs1726654; hg19: chr1-236417723;