2-171522147-T-A

Variant names:

• chr2-171522147-T-A
• rs884409
• NM_001256909.2:c.-126T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001256909.2(CYBRD1):​c.-126T>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000324 in 1,233,400 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: CYBRD1 NM_001256909.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256909.2. 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
	CYBRD1	NM_001256909.2		c.-126T>A		upstream_gene	N/A	NP_001243838.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBRD1	ENST00000409484.5	TSL:2	c.-126T>A		upstream_gene	N/A	ENSP00000386739.1
	CYBRD1	ENST00000468308.1	TSL:3	n.-201T>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000324 AC: 4 AN: 1233400 Hom.: 0 AF XY: 0.00000329 AC XY: 2 AN XY: 607060

African (AFR) AF: 0.000143 AC: 4 AN: 27890

American (AMR) AF: 0.00 AC: 0 AN: 29300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20990

East Asian (EAS) AF: 0.00 AC: 0 AN: 34542

South Asian (SAS) AF: 0.00 AC: 0 AN: 66678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5224

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 952878

Other (OTH) AF: 0.00 AC: 0 AN: 52202

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.4
DANN	Benign	0.53
PhyloP100		0.25
PromoterAI		0.045	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs884409; hg19: chr2-172378657;