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GeneBe

17-63436148-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001915.4(CYB561):c.207G>A(p.Leu69=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,613,808 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 14 hom., cov: 33)
Exomes 𝑓: 0.00069 ( 14 hom. )

Consequence

CYB561
NM_001915.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.988
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-63436148-C-T is Benign according to our data. Variant chr17-63436148-C-T is described in ClinVar as [Benign]. Clinvar id is 3034465.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.988 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00706 (1075/152318) while in subpopulation AFR AF= 0.0245 (1020/41572). AF 95% confidence interval is 0.0233. There are 14 homozygotes in gnomad4. There are 501 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYB561NM_001915.4 linkuse as main transcriptc.207G>A p.Leu69= synonymous_variant 3/6 ENST00000360793.8
CYB561NM_001330421.2 linkuse as main transcriptc.228G>A p.Leu76= synonymous_variant 3/6
CYB561NM_001017916.2 linkuse as main transcriptc.207G>A p.Leu69= synonymous_variant 3/6
CYB561NM_001017917.2 linkuse as main transcriptc.207G>A p.Leu69= synonymous_variant 3/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYB561ENST00000360793.8 linkuse as main transcriptc.207G>A p.Leu69= synonymous_variant 3/61 NM_001915.4 P1P49447-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00704
AC:
1071
AN:
152200
Hom.:
13
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0245
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00268
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000413
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00180
AC:
451
AN:
250672
Hom.:
7
AF XY:
0.00149
AC XY:
202
AN XY:
135594
show subpopulations
Gnomad AFR exome
AF:
0.0245
Gnomad AMR exome
AF:
0.00124
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.000686
AC:
1002
AN:
1461490
Hom.:
14
Cov.:
32
AF XY:
0.000612
AC XY:
445
AN XY:
727036
show subpopulations
Gnomad4 AFR exome
AF:
0.0249
Gnomad4 AMR exome
AF:
0.00141
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00157
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00706
AC:
1075
AN:
152318
Hom.:
14
Cov.:
33
AF XY:
0.00673
AC XY:
501
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0245
Gnomad4 AMR
AF:
0.00268
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00144
Hom.:
1
Bravo
AF:
0.00772
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

CYB561-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 18, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
Cadd
Benign
15
Dann
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35447397; hg19: chr17-61513509; API