chr1-236256198-A-G

Variant names:

• chr1-236256198-A-G
• rs1405633
• NM_019891.4:c.223-2693T>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.223-2693T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,902 control chromosomes in the GnomAD database, including 8,194 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 0.32 (8194 hom., cov: 32)
• Consequence: ERO1B NM_019891.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERO1B	NM_019891.4	c.223-2693T>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.223-2693T>C		intron_variant	Intron 2 of 15	1	NM_019891.4	ENSP00000346635.5

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47965 AN: 151784 Hom.: 8175 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.316 AC: 48018 AN: 151902 Hom.: 8194 Cov.: 32 AF XY: 0.323 AC XY: 23986 AN XY: 74264

African (AFR) AF: 0.301 AC: 12460 AN: 41440

American (AMR) AF: 0.358 AC: 5458 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 906 AN: 3464

East Asian (EAS) AF: 0.773 AC: 3963 AN: 5130

South Asian (SAS) AF: 0.306 AC: 1471 AN: 4812

European-Finnish (FIN) AF: 0.387 AC: 4090 AN: 10566

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.276 AC: 18724 AN: 67918

Other (OTH) AF: 0.319 AC: 673 AN: 2110

Alfa AF: 0.296 Hom.: 811

Bravo AF: 0.321

Asia WGS AF: 0.533 AC: 1850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.3
DANN	Benign	0.79
PhyloP100		0.16
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: rs1405633; hg19: chr1-236419498;