rs10455

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024843.4(CYBRD1):c.797G>A(p.Ser266Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 1,613,702 control chromosomes in the GnomAD database, including 361,957 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 39429 hom., cov: 32)

Exomes 𝑓: 0.66 ( 322528 hom. )

Consequence

CYBRD1
NM_024843.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.08

Publications

43 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.5515926E-7).

BP6

Variant 2-171554763-G-A is Benign according to our data. Variant chr2-171554763-G-A is described in ClinVar as Benign. ClinVar VariationId is 1237711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBRD1	NM_024843.4 link	c.797G>A	p.Ser266Asn	missense_variant	Exon 4 of 4	ENST00000321348.9	NP_079119.3	Q53TN4-1
CYBRD1	NM_001256909.2 link	c.623G>A	p.Ser208Asn	missense_variant	Exon 4 of 4		NP_001243838.1	Q53TN4-3
CYBRD1	NM_001127383.2 link	c.*114G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001120855.1	Q53TN4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYBRD1	ENST00000321348.9 link	c.797G>A	p.Ser266Asn	missense_variant	Exon 4 of 4	1	NM_024843.4	ENSP00000319141.4	Q53TN4-1
CYBRD1	ENST00000375252.3 link	c.*114G>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000364401.3	Q53TN4-2
CYBRD1	ENST00000409484.5 link	c.623G>A	p.Ser208Asn	missense_variant	Exon 4 of 4	2		ENSP00000386739.1	Q53TN4-3
CYBRD1	ENST00000445146.1 link	c.*156G>A		downstream_gene_variant		3		ENSP00000402242.1	C9JML1

Frequencies

GnomAD3 genomes

AF:

0.709

AC:

107792

AN:

151952

Hom.:

39385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.883

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.635

Gnomad ASJ

AF:

0.590

Gnomad EAS

AF:

0.380

Gnomad SAS

AF:

0.671

Gnomad FIN

AF:

0.617

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.656

GnomAD2 exomes

AF:

0.641

AC:

160756

AN:

250712

AF XY:

0.641

show subpopulations

Gnomad AFR exome

AF:

0.888

Gnomad AMR exome

AF:

0.579

Gnomad ASJ exome

AF:

0.589

Gnomad EAS exome

AF:

0.375

Gnomad FIN exome

AF:

0.626

Gnomad NFE exome

AF:

0.671

Gnomad OTH exome

AF:

0.632

GnomAD4 exome

AF:

0.661

AC:

965561

AN:

1461628

Hom.:

322528

Cov.:

AF XY:

0.659

AC XY:

479435

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.889

AC:

29736

AN:

33466

American (AMR)

AF:

0.583

AC:

26045

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.589

AC:

15389

AN:

26132

East Asian (EAS)

AF:

0.370

AC:

14669

AN:

39680

South Asian (SAS)

AF:

0.653

AC:

56325

AN:

86252

European-Finnish (FIN)

AF:

0.632

AC:

33748

AN:

53412

Middle Eastern (MID)

AF:

0.523

AC:

3009

AN:

5748

European-Non Finnish (NFE)

AF:

0.672

AC:

747492

AN:

1111854

Other (OTH)

AF:

0.648

AC:

39148

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

18830

37660

56491

75321

94151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19260

38520

57780

77040

96300

<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:

0.710

AC:

107897

AN:

152074

Hom.:

39429

Cov.:

AF XY:

0.706

AC XY:

52437

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.883

AC:

36668

AN:

41504

American (AMR)

AF:

0.635

AC:

9691

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

2045

AN:

3468

East Asian (EAS)

AF:

0.380

AC:

1962

AN:

5168

South Asian (SAS)

AF:

0.670

AC:

3228

AN:

4818

European-Finnish (FIN)

AF:

0.617

AC:

6508

AN:

10556

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.671

AC:

45626

AN:

67972

Other (OTH)

AF:

0.654

AC:

1384

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1529

3058

4586

6115

7644

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:

0.671

Hom.:

157964

Bravo

AF:

0.711

TwinsUK

AF:

0.684

AC:

2536

ALSPAC

AF:

0.672

AC:

2589

ESP6500AA

AF:

0.879

AC:

3875

ESP6500EA

AF:

0.659

AC:

5670

ExAC

AF:

0.651

AC:

79072

Asia WGS

AF:

0.595

AC:

2070

AN:

3478

EpiCase

AF:

0.657

EpiControl

AF:

0.659

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 04, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.13

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.085

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.14

T;T

MetaRNN

Benign

5.6e-7

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.28

.;N

PhyloP100

-1.1

PrimateAI

Benign

0.27

PROVEAN

Benign

0.060

N;N

REVEL

Benign

0.12

Sift

Benign

0.93

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.0

.;B

Vest4

0.045

MPC

0.37

ClinPred

0.0015

GERP RS

-3.3

Varity_R

0.026

gMVP

0.21

Mutation Taster

=93/7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over