rs1749569

Variant names:

• chr1-236256281-T-G
• rs1749569
• NM_019891.4:c.223-2776A>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.223-2776A>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
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019891.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERO1B	NM_019891.4	MANE Select	c.223-2776A>C		intron	N/A	NP_063944.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERO1B	ENST00000354619.10	TSL:1 MANE Select	c.223-2776A>C		intron	N/A	ENSP00000346635.5	Q86YB8-1
	ERO1B	ENST00000687487.1		c.-135-2776A>C		intron	N/A	ENSP00000510551.1	A0A8I5KWQ1
	ERO1B	ENST00000366589.1	TSL:5	n.256-2776A>C		intron	N/A

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

African (AFR) AF: 0.200 AC: 8283 AN: 41478

American (AMR) AF: 0.283 AC: 4322 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 771 AN: 3464

East Asian (EAS) AF: 0.381 AC: 1962 AN: 5148

South Asian (SAS) AF: 0.199 AC: 956 AN: 4816

European-Finnish (FIN) AF: 0.360 AC: 3794 AN: 10544

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

European-Non Finnish (NFE) AF: 0.248 AC: 16852 AN: 67938

Other (OTH) AF: 0.254 AC: 536 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.52
PhyloP100		-1.2
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: rs1749569; hg19: chr1-236419581;