Genetic Variant CYB561:c.203-542C>T (chr17-63436694-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_001915.4(CYB561):c.203-542C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 160,042 control chromosomes in the GnomAD database, including 4,304 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 0.23 ( 4077 hom., cov: 32)

Exomes 𝑓: 0.23 ( 227 hom. )

Consequence

CYB561
NM_001915.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.468

Publications

6 publications found

Variant links:

Genes affected

CYB561 (HGNC:2571): (cytochrome b561) Predicted to enable transmembrane monodehydroascorbate reductase activity. Predicted to be involved in ascorbate homeostasis. Predicted to be located in chromaffin granule membrane. Predicted to be active in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

CYB561 Gene-Disease associations (from GenCC):

orthostatic hypotension 2
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CYB561 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=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CYB561	NM_001915.4 link	c.203-542C>T	intron_variant	Intron 2 of 5	ENST00000360793.8	NP_001906.3	P49447-1
CYB561	NM_001330421.2 link	c.224-542C>T	intron_variant	Intron 2 of 5		NP_001317350.1	P49447J3QRH5
CYB561	NM_001017916.2 link	c.203-542C>T	intron_variant	Intron 2 of 5		NP_001017916.1	P49447-1B3KTA1
CYB561	NM_001017917.2 link	c.203-542C>T	intron_variant	Intron 2 of 5		NP_001017917.1	P49447-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB561	ENST00000360793.8 link	c.203-542C>T		intron_variant	Intron 2 of 5	1	NM_001915.4	ENSP00000354028.3		P49447-1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34796

AN:

152016

Hom.:

4072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.0854

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.232

AC:

1836

AN:

7908

Hom.:

227

Cov.:

AF XY:

0.242

AC XY:

978

AN XY:

4048

show subpopulations

African (AFR)

AF:

0.0833

AC:

AN:

American (AMR)

AF:

0.231

AC:

462

AN:

2002

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

AN:

East Asian (EAS)

AF:

0.111

AC:

AN:

262

South Asian (SAS)

AF:

0.300

AC:

278

AN:

928

European-Finnish (FIN)

AF:

0.273

AC:

AN:

Middle Eastern (MID)

AF:

0.200

AC:

AN:

European-Non Finnish (NFE)

AF:

0.229

AC:

975

AN:

4252

Other (OTH)

AF:

0.204

AC:

AN:

284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

135

202

270

337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.229

AC:

34805

AN:

152134

Hom.:

4077

Cov.:

AF XY:

0.232

AC XY:

17248

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.218

AC:

9035

AN:

41504

American (AMR)

AF:

0.237

AC:

3627

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

829

AN:

3472

East Asian (EAS)

AF:

0.0858

AC:

442

AN:

5150

South Asian (SAS)

AF:

0.302

AC:

1458

AN:

4826

European-Finnish (FIN)

AF:

0.266

AC:

2807

AN:

10568

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.234

AC:

15883

AN:

68004

Other (OTH)

AF:

0.216

AC:

455

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1393

2786

4179

5572

6965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.234

Hom.:

1573

Bravo

AF:

0.223

Asia WGS

AF:

0.189

AC:

658

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.3

(source)

DANN

Benign

0.51

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

Other links and lift over