dbSNP rs3731976: CYBRD1:n.36G>A (chr2-171522383-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000468308.1(CYBRD1):n.36G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,492,180 control chromosomes in the GnomAD database, including 126,752 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 0.42 ( 14030 hom., cov: 32)

Exomes 𝑓: 0.40 ( 112722 hom. )

Consequence

CYBRD1
ENST00000468308.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.988

Publications

12 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CYBRD1	NM_001256909.2 link	c.19+92G>A	intron_variant	Intron 1 of 3		NP_001243838.1	Q53TN4-3
CYBRD1	NM_024843.4 link	c.-163G>A	upstream_gene_variant		ENST00000321348.9	NP_079119.3	Q53TN4-1
CYBRD1	NM_001127383.2 link	c.-163G>A	upstream_gene_variant			NP_001120855.1	Q53TN4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBRD1	ENST00000321348.9 link	c.-163G>A		upstream_gene_variant		1	NM_024843.4	ENSP00000319141.4		Q53TN4-1

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64455

AN:

151822

Hom.:

14012

Cov.:

show subpopulations

Gnomad AFR

AF:

0.453

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.483

Gnomad ASJ

AF:

0.439

Gnomad EAS

AF:

0.712

Gnomad SAS

AF:

0.503

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.384

Gnomad OTH

AF:

0.423

GnomAD4 exome

AF:

0.404

AC:

541711

AN:

1340240

Hom.:

112722

Cov.:

AF XY:

0.406

AC XY:

266067

AN XY:

655686

show subpopulations

African (AFR)

AF:

0.464

AC:

13737

AN:

29600

American (AMR)

AF:

0.533

AC:

14194

AN:

26612

Ashkenazi Jewish (ASJ)

AF:

0.449

AC:

9721

AN:

21630

East Asian (EAS)

AF:

0.720

AC:

25364

AN:

35206

South Asian (SAS)

AF:

0.486

AC:

34041

AN:

69994

European-Finnish (FIN)

AF:

0.332

AC:

14406

AN:

43334

Middle Eastern (MID)

AF:

0.394

AC:

2010

AN:

5102

European-Non Finnish (NFE)

AF:

0.385

AC:

405136

AN:

1053466

Other (OTH)

AF:

0.418

AC:

23102

AN:

55296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

19453

38905

58358

77810

97263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13282

26564

39846

53128

66410

<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:

0.425

AC:

64516

AN:

151940

Hom.:

14030

Cov.:

AF XY:

0.426

AC XY:

31643

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.453

AC:

18781

AN:

41446

American (AMR)

AF:

0.484

AC:

7394

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

1520

AN:

3466

East Asian (EAS)

AF:

0.712

AC:

3645

AN:

5122

South Asian (SAS)

AF:

0.502

AC:

2422

AN:

4822

European-Finnish (FIN)

AF:

0.316

AC:

3343

AN:

10566

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.384

AC:

26100

AN:

67918

Other (OTH)

AF:

0.421

AC:

890

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1950

3900

5850

7800

9750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.412

Hom.:

1597

Bravo

AF:

0.442

Asia WGS

AF:

0.555

AC:

1933

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.8

(source)

DANN

Benign

0.84

PhyloP100

0.99

PromoterAI

-0.12

Neutral

(source)

Mutation Taster

=300/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over