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GeneBe

17-63437524-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001915.4(CYB561):c.24C>T(p.Ala8=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,611,874 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 4 hom. )

Consequence

CYB561
NM_001915.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.11
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 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=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-63437524-G-A is Benign according to our data. Variant chr17-63437524-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3060907.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=-1.11 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYB561NM_001915.4 linkuse as main transcriptc.24C>T p.Ala8= synonymous_variant 2/6 ENST00000360793.8
CYB561NM_001330421.2 linkuse as main transcriptc.45C>T p.Ala15= synonymous_variant 2/6
CYB561NM_001017916.2 linkuse as main transcriptc.24C>T p.Ala8= synonymous_variant 2/6
CYB561NM_001017917.2 linkuse as main transcriptc.24C>T p.Ala8= synonymous_variant 2/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYB561ENST00000360793.8 linkuse as main transcriptc.24C>T p.Ala8= synonymous_variant 2/61 NM_001915.4 P1P49447-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00146
AC:
222
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000458
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00150
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.000753
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00244
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.00141
AC:
347
AN:
245880
Hom.:
0
AF XY:
0.00145
AC XY:
194
AN XY:
133594
show subpopulations
Gnomad AFR exome
AF:
0.000504
Gnomad AMR exome
AF:
0.00134
Gnomad ASJ exome
AF:
0.000100
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.000648
Gnomad NFE exome
AF:
0.00233
Gnomad OTH exome
AF:
0.00198
GnomAD4 exome
AF:
0.00213
AC:
3108
AN:
1459560
Hom.:
4
Cov.:
31
AF XY:
0.00210
AC XY:
1528
AN XY:
726218
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
Gnomad4 AMR exome
AF:
0.00123
Gnomad4 ASJ exome
AF:
0.0000766
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000475
Gnomad4 FIN exome
AF:
0.000735
Gnomad4 NFE exome
AF:
0.00254
Gnomad4 OTH exome
AF:
0.00216
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00145
AC:
221
AN:
152314
Hom.:
0
Cov.:
32
AF XY:
0.00144
AC XY:
107
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.000457
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.000753
Gnomad4 NFE
AF:
0.00244
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.00240
Hom.:
0
Bravo
AF:
0.00175
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00289
EpiControl
AF:
0.00285

ClinVar

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

Submissions by phenotype

CYB561-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 07, 2019This variant is classified as likely 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
-0.80
Cadd
Benign
2.5
Dann
Benign
0.66
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.6

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

LitVar

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

Other links and lift over

dbSNP: rs140356224; hg19: chr17-61514885; API