2-171522147-T-G

Variant names:

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

Variant summary

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

The NM_001256909.2(CYBRD1):​c.-126T>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,384,136 control chromosomes in the GnomAD database, including 21,364 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 0.22 (4284 hom., cov: 32)
  • Exomes 𝑓: 0.16 (17080 hom.)
• Consequence: CYBRD1 NM_001256909.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 19 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBRD1	NM_001256909.2	c.-126T>G		upstream_gene_variant			NP_001243838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBRD1	ENST00000409484.5	c.-126T>G		upstream_gene_variant		2		ENSP00000386739.1
CYBRD1	ENST00000468308.1	n.-201T>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33356 AN: 151988 Hom.: 4272 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.161 AC: 198219 AN: 1232030 Hom.: 17080 AF XY: 0.160 AC XY: 97119 AN XY: 606360

African (AFR) AF: 0.359 AC: 9990 AN: 27844

American (AMR) AF: 0.0933 AC: 2733 AN: 29278

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 2511 AN: 20982

East Asian (EAS) AF: 0.123 AC: 4233 AN: 34526

South Asian (SAS) AF: 0.155 AC: 10328 AN: 66598

European-Finnish (FIN) AF: 0.235 AC: 10249 AN: 43646

Middle Eastern (MID) AF: 0.136 AC: 712 AN: 5224

European-Non Finnish (NFE) AF: 0.156 AC: 148651 AN: 951774

Other (OTH) AF: 0.169 AC: 8812 AN: 52158

GnomAD4 genome AF: 0.220 AC: 33398 AN: 152106 Hom.: 4284 Cov.: 32 AF XY: 0.221 AC XY: 16410 AN XY: 74352

African (AFR) AF: 0.358 AC: 14831 AN: 41450

American (AMR) AF: 0.152 AC: 2317 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3470

East Asian (EAS) AF: 0.140 AC: 728 AN: 5186

South Asian (SAS) AF: 0.161 AC: 775 AN: 4826

European-Finnish (FIN) AF: 0.249 AC: 2630 AN: 10570

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11121 AN: 67996

Other (OTH) AF: 0.188 AC: 398 AN: 2114

Alfa AF: 0.195 Hom.: 1196

Bravo AF: 0.218

Asia WGS AF: 0.156 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.7
DANN	Benign	0.42
PhyloP100		0.25
PromoterAI		0.15	Neutral
Mutation Taster		=100/0	polymorphism

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;