dbSNP rs3087776: CYB561:c.*1485G>A (chr17-63432917-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_001915.4(CYB561):c.*1485G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,628 control chromosomes in the GnomAD database, including 23,413 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 0.54 ( 23340 hom., cov: 32)

Exomes 𝑓: 0.48 ( 73 hom. )

Consequence

CYB561
NM_001915.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.839

Publications

21 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

new If you want to explore the variant's impact on the transcript NM_001915.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001915.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYB561	NM_001915.4	MANE Select	c.*1485G>A	3_prime_UTR	Exon 6 of 6	NP_001906.3
CYB561	NM_001330421.2		c.*1485G>A	3_prime_UTR	Exon 6 of 6	NP_001317350.1	J3QRH5
CYB561	NM_001017916.2		c.*1485G>A	3_prime_UTR	Exon 6 of 6	NP_001017916.1	P49447-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYB561	ENST00000360793.8	TSL:1 MANE Select	c.*1485G>A	3_prime_UTR	Exon 6 of 6	ENSP00000354028.3	P49447-1
CYB561	ENST00000392975.6	TSL:1	c.*1485G>A	3_prime_UTR	Exon 6 of 6	ENSP00000376701.2	P49447-1
CYB561	ENST00000392976.5	TSL:3	c.*1485G>A	3_prime_UTR	Exon 6 of 6	ENSP00000376702.1	P49447-1

Frequencies

GnomAD3 genomes

AF:

0.540

AC:

81976

AN:

151938

Hom.:

23329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.707

Gnomad AMI

AF:

0.596

Gnomad AMR

AF:

0.450

Gnomad ASJ

AF:

0.469

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.496

Gnomad OTH

AF:

0.496

GnomAD4 exome

AF:

0.476

AC:

272

AN:

572

Hom.:

Cov.:

AF XY:

0.456

AC XY:

145

AN XY:

318

show subpopulations

African (AFR)

AF:

0.813

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.472

AC:

182

AN:

386

Other (OTH)

AF:

0.619

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.539

AC:

82023

AN:

152056

Hom.:

23340

Cov.:

AF XY:

0.535

AC XY:

39762

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.707

AC:

29304

AN:

41466

American (AMR)

AF:

0.450

AC:

6881

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

1629

AN:

3470

East Asian (EAS)

AF:

0.153

AC:

792

AN:

5174

South Asian (SAS)

AF:

0.483

AC:

2322

AN:

4812

European-Finnish (FIN)

AF:

0.537

AC:

5671

AN:

10558

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.496

AC:

33715

AN:

67972

Other (OTH)

AF:

0.491

AC:

1035

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1858

3717

5575

7434

9292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.499

Hom.:

24720

Bravo

AF:

0.536

Asia WGS

AF:

0.362

AC:

1262

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.63

(source)

DANN

Benign

0.41

PhyloP100

-0.84

Mutation Taster

=84/16

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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