2-171522379-C-G

Variant names:

• chr2-171522379-C-G
• rs2356782
• ENST00000468308.1:n.32C>G

Variant summary

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

The ENST00000468308.1(CYBRD1):​n.32C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,491,972 control chromosomes in the GnomAD database, including 247,693 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 0.63 (31392 hom., cov: 32)
  • Exomes 𝑓: 0.56 (216301 hom.)
• Consequence: CYBRD1 ENST00000468308.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• Publications: 8 publications found

Genes affected

CYBRD1 (HGNC:20797): (cytochrome b reductase 1) This gene is a member of the cytochrome b(561) family that encodes an iron-regulated protein. It highly expressed in the duodenal brush border membrane. It has ferric reductase activity and is believed to play a physiological role in dietary iron absorption. [provided by RefSeq, Jul 2008]

CYBRD1 Gene-Disease associations (from GenCC):

• hereditary hemochromatosis

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000468308.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBRD1	NM_001256909.2		c.19+88C>G		intron	N/A	NP_001243838.1
	CYBRD1	NM_024843.4	MANE Select	c.-167C>G		upstream_gene	N/A	NP_079119.3
	CYBRD1	NM_001127383.2		c.-167C>G		upstream_gene	N/A	NP_001120855.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBRD1	ENST00000468308.1	TSL:3	n.32C>G		non_coding_transcript_exon	Exon 1 of 3
	CYBRD1	ENST00000409484.5	TSL:2	c.19+88C>G		intron	N/A	ENSP00000386739.1
	CYBRD1	ENST00000321348.9	TSL:1 MANE Select	c.-167C>G		upstream_gene	N/A	ENSP00000319141.4

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96324 AN: 151808 Hom.: 31359 Cov.: 32

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.564 AC: 755754 AN: 1340046 Hom.: 216301 Cov.: 60 AF XY: 0.565 AC XY: 370307 AN XY: 655288

African (AFR) AF: 0.785 AC: 23243 AN: 29624

American (AMR) AF: 0.627 AC: 16787 AN: 26764

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 12229 AN: 21570

East Asian (EAS) AF: 0.843 AC: 29674 AN: 35184

South Asian (SAS) AF: 0.643 AC: 44892 AN: 69774

European-Finnish (FIN) AF: 0.569 AC: 24858 AN: 43694

Middle Eastern (MID) AF: 0.531 AC: 2721 AN: 5128

European-Non Finnish (NFE) AF: 0.540 AC: 569081 AN: 1052992

Other (OTH) AF: 0.583 AC: 32269 AN: 55316

GnomAD4 genome AF: 0.635 AC: 96414 AN: 151926 Hom.: 31392 Cov.: 32 AF XY: 0.637 AC XY: 47348 AN XY: 74272

African (AFR) AF: 0.778 AC: 32225 AN: 41446

American (AMR) AF: 0.632 AC: 9653 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1945 AN: 3470

East Asian (EAS) AF: 0.853 AC: 4367 AN: 5118

South Asian (SAS) AF: 0.663 AC: 3195 AN: 4816

European-Finnish (FIN) AF: 0.565 AC: 5975 AN: 10572

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37202 AN: 67906

Other (OTH) AF: 0.597 AC: 1263 AN: 2114

Alfa AF: 0.501 Hom.: 1517

Bravo AF: 0.648

Asia WGS AF: 0.708 AC: 2463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.0
DANN	Benign	0.74
PhyloP100		-0.20
PromoterAI		-0.11	Neutral
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: rs2356782; hg19: chr2-172378889;