rs2058203

Variant names:

• chr17-63445643-C-G
• rs2058203
• NM_001915.4:c.-14+602G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYB561	NM_001915.4	c.-14+602G>C		intron_variant	Intron 1 of 5	ENST00000360793.8	NP_001906.3
CYB561	NM_001017916.2	c.-14+255G>C		intron_variant	Intron 1 of 5		NP_001017916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB561	ENST00000360793.8	c.-14+602G>C		intron_variant	Intron 1 of 5	1	NM_001915.4	ENSP00000354028.3

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

African (AFR) AF: 0.643 AC: 26627 AN: 41416

American (AMR) AF: 0.439 AC: 6708 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3466

East Asian (EAS) AF: 0.149 AC: 770 AN: 5152

South Asian (SAS) AF: 0.461 AC: 2226 AN: 4826

European-Finnish (FIN) AF: 0.532 AC: 5619 AN: 10564

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.486 AC: 33028 AN: 67896

Other (OTH) AF: 0.469 AC: 991 AN: 2112

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
PhyloP100		-0.033
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2058203; hg19: chr17-61523004;