rs2015356

Positions:

• chr17-63436694-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB561	NM_001915.4	c.203-542C>T		intron_variant		ENST00000360793.8	NP_001906.3
CYB561	NM_001017916.2	c.203-542C>T		intron_variant			NP_001017916.1
CYB561	NM_001017917.2	c.203-542C>T		intron_variant			NP_001017917.1
CYB561	NM_001330421.2	c.224-542C>T		intron_variant			NP_001317350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB561	ENST00000360793.8	c.203-542C>T		intron_variant		1	NM_001915.4	ENSP00000354028	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34796 AN: 152016 Hom.: 4072 Cov.: 32

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.: 0 AF XY: 0.242 AC XY: 978 AN XY: 4048

Gnomad4 AFR exome AF: 0.0833

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.229 AC: 34805 AN: 152134 Hom.: 4077 Cov.: 32 AF XY: 0.232 AC XY: 17248 AN XY: 74352

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.0858

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.216

Alfa AF: 0.235 Hom.: 971

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
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs2015356; hg19: chr17-61514055;