rs2058203

Positions:

• chr17-63445643-C-G

Variant summary

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

The NM_001915.4(CYB561):​c.-14+602G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,910 control chromosomes in the GnomAD database, including 20,963 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 0.51 (20963 hom., cov: 31)
• Consequence: CYB561 NM_001915.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB561	NM_001915.4	c.-14+602G>C		intron_variant		ENST00000360793.8
CYB561	NM_001017916.2	c.-14+255G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB561	ENST00000360793.8	c.-14+602G>C		intron_variant		1	NM_001915.4	P1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78177 AN: 151790 Hom.: 20958 Cov.: 31

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.475

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.515 AC: 78205 AN: 151910 Hom.: 20963 Cov.: 31 AF XY: 0.512 AC XY: 38008 AN XY: 74246

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.469

Alfa AF: 0.520 Hom.: 2583

Bravo AF: 0.510

Asia WGS AF: 0.333 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2058203; hg19: chr17-61523004;