rs13009270

Variant names:

• chr2-171546027-C-A
• rs13009270
• NM_024843.4:c.402+4234C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-171546027-C-A
• chr2-171546027-C-G

Variant summary

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

The NM_024843.4(CYBRD1):​c.402+4234C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,144 control chromosomes in the GnomAD database, including 2,311 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 0.17 (2311 hom., cov: 31)
• Consequence: CYBRD1 NM_024843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024843.4. 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_024843.4	MANE Select	c.402+4234C>A		intron	N/A	NP_079119.3
	CYBRD1	NM_001256909.2		c.228+4234C>A		intron	N/A	NP_001243838.1
	CYBRD1	NM_001127383.2		c.194-7319C>A		intron	N/A	NP_001120855.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBRD1	ENST00000321348.9	TSL:1 MANE Select	c.402+4234C>A		intron	N/A	ENSP00000319141.4
	CYBRD1	ENST00000375252.3	TSL:1	c.194-7319C>A		intron	N/A	ENSP00000364401.3
	CYBRD1	ENST00000409484.5	TSL:2	c.228+4234C>A		intron	N/A	ENSP00000386739.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25902 AN: 152026 Hom.: 2310 Cov.: 31

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.170 AC: 25912 AN: 152144 Hom.: 2311 Cov.: 31 AF XY: 0.174 AC XY: 12913 AN XY: 74366

African (AFR) AF: 0.172 AC: 7128 AN: 41504

American (AMR) AF: 0.134 AC: 2046 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3466

East Asian (EAS) AF: 0.0594 AC: 308 AN: 5182

South Asian (SAS) AF: 0.167 AC: 805 AN: 4824

European-Finnish (FIN) AF: 0.250 AC: 2646 AN: 10568

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12019 AN: 68006

Other (OTH) AF: 0.154 AC: 325 AN: 2114

Alfa AF: 0.167 Hom.: 6554

Bravo AF: 0.160

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.66
PhyloP100		0.33
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: rs13009270; hg19: chr2-172402537;