dbSNP rs960748: CYBRD1:c.193+688G>A (chr2-171523426-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 NM_024843.4(CYBRD1):c.193+688G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 220,412 control chromosomes in the GnomAD database, including 39,638 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 0.62 ( 30220 hom., cov: 32)

Exomes 𝑓: 0.52 ( 9418 hom. )

Consequence

CYBRD1
NM_024843.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.244

Publications

24 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=-0.75).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 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	UniProt
CYBRD1	NM_024843.4	MANE Select	c.193+688G>A	intron	N/A	NP_079119.3
CYBRD1	NM_001256909.2		c.19+1135G>A	intron	N/A	NP_001243838.1	Q53TN4-3
CYBRD1	NM_001127383.2		c.193+688G>A	intron	N/A	NP_001120855.1	Q53TN4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYBRD1	ENST00000321348.9	TSL:1 MANE Select	c.193+688G>A	intron	N/A	ENSP00000319141.4	Q53TN4-1
CYBRD1	ENST00000375252.3	TSL:1	c.193+688G>A	intron	N/A	ENSP00000364401.3	Q53TN4-2
CYBRD1	ENST00000858692.1		c.193+688G>A	intron	N/A	ENSP00000528751.1

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94747

AN:

151936

Hom.:

30188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.747

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.556

Gnomad EAS

AF:

0.854

Gnomad SAS

AF:

0.637

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.591

GnomAD4 exome

AF:

0.516

AC:

35252

AN:

68358

Hom.:

9418

AF XY:

0.522

AC XY:

19686

AN XY:

37714

show subpopulations

African (AFR)

AF:

0.645

AC:

218

AN:

338

American (AMR)

AF:

0.519

AC:

355

AN:

684

Ashkenazi Jewish (ASJ)

AF:

0.530

AC:

605

AN:

1142

East Asian (EAS)

AF:

0.876

AC:

177

AN:

202

South Asian (SAS)

AF:

0.544

AC:

7994

AN:

14702

European-Finnish (FIN)

AF:

0.550

AC:

7822

AN:

14218

Middle Eastern (MID)

AF:

0.515

AC:

925

AN:

1796

European-Non Finnish (NFE)

AF:

0.484

AC:

15718

AN:

32482

Other (OTH)

AF:

0.515

AC:

1438

AN:

2794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

766

1532

2298

3064

3830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.624

AC:

94836

AN:

152054

Hom.:

30220

Cov.:

AF XY:

0.627

AC XY:

46571

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.747

AC:

30987

AN:

41492

American (AMR)

AF:

0.625

AC:

9555

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.556

AC:

1929

AN:

3468

East Asian (EAS)

AF:

0.853

AC:

4401

AN:

5158

South Asian (SAS)

AF:

0.636

AC:

3069

AN:

4822

European-Finnish (FIN)

AF:

0.568

AC:

5997

AN:

10564

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.546

AC:

37066

AN:

67938

Other (OTH)

AF:

0.587

AC:

1239

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1780

3560

5339

7119

8899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<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:

0.568

Hom.:

101749

Bravo

AF:

0.636

Asia WGS

AF:

0.702

AC:

2441

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.7

(source)

DANN

Benign

0.84

PhyloP100

0.24

PromoterAI

0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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