dbSNP rs2542941: CYBRD1:c.403-135C>T (chr2-171553211-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024843.4(CYBRD1):c.403-135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 983,600 control chromosomes in the GnomAD database, including 218,768 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 0.70 ( 38040 hom., cov: 33)

Exomes 𝑓: 0.65 ( 180728 hom. )

Consequence

CYBRD1
NM_024843.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.687

Publications

10 publications found

Variant links:

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

CYBRD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYBRD1	NM_024843.4	MANE Select	c.403-135C>T	intron	N/A	NP_079119.3
CYBRD1	NM_001256909.2		c.229-135C>T	intron	N/A	NP_001243838.1
CYBRD1	NM_001127383.2		c.194-135C>T	intron	N/A	NP_001120855.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYBRD1	ENST00000321348.9	TSL:1 MANE Select	c.403-135C>T	intron	N/A	ENSP00000319141.4
CYBRD1	ENST00000375252.3	TSL:1	c.194-135C>T	intron	N/A	ENSP00000364401.3
CYBRD1	ENST00000858692.1		c.403-135C>T	intron	N/A	ENSP00000528751.1

Frequencies

GnomAD3 genomes

AF:

0.699

AC:

106228

AN:

152014

Hom.:

38005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.845

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.632

Gnomad ASJ

AF:

0.590

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.676

Gnomad FIN

AF:

0.617

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.645

GnomAD4 exome

AF:

0.655

AC:

544604

AN:

831468

Hom.:

180728

AF XY:

0.654

AC XY:

279536

AN XY:

427284

show subpopulations

African (AFR)

AF:

0.846

AC:

16551

AN:

19568

American (AMR)

AF:

0.590

AC:

16284

AN:

27602

Ashkenazi Jewish (ASJ)

AF:

0.591

AC:

11260

AN:

19064

East Asian (EAS)

AF:

0.371

AC:

12076

AN:

32562

South Asian (SAS)

AF:

0.658

AC:

38576

AN:

58584

European-Finnish (FIN)

AF:

0.634

AC:

22702

AN:

35816

Middle Eastern (MID)

AF:

0.542

AC:

1601

AN:

2952

European-Non Finnish (NFE)

AF:

0.671

AC:

400573

AN:

596622

Other (OTH)

AF:

0.646

AC:

24981

AN:

38698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

8830

17661

26491

35322

44152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7946

15892

23838

31784

39730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.699

AC:

106321

AN:

152132

Hom.:

38040

Cov.:

AF XY:

0.695

AC XY:

51682

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.845

AC:

35099

AN:

41530

American (AMR)

AF:

0.632

AC:

9653

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

2047

AN:

3468

East Asian (EAS)

AF:

0.382

AC:

1978

AN:

5176

South Asian (SAS)

AF:

0.675

AC:

3253

AN:

4820

European-Finnish (FIN)

AF:

0.617

AC:

6517

AN:

10556

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.671

AC:

45630

AN:

67984

Other (OTH)

AF:

0.644

AC:

1360

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1590

3180

4770

6360

7950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.669

Hom.:

56527

Bravo

AF:

0.699

Asia WGS

AF:

0.595

AC:

2070

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.11

(source)

DANN

Benign

0.29

PhyloP100

-0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over