rs3087776

Positions:

• chr17-63432917-C-T

Variant summary

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

The NM_001915.4(CYB561):​c.*1485G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,628 control chromosomes in the GnomAD database, including 23,413 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 0.54 (23340 hom., cov: 32)
  • Exomes 𝑓: 0.48 (73 hom.)
• Consequence: CYB561 NM_001915.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.839

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB561	NM_001915.4	c.*1485G>A		3_prime_UTR_variant	6/6	ENST00000360793.8	NP_001906.3
CYB561	NM_001330421.2	c.*1485G>A		3_prime_UTR_variant	6/6		NP_001317350.1
CYB561	NM_001017916.2	c.*1485G>A		3_prime_UTR_variant	6/6		NP_001017916.1
CYB561	NM_001017917.2	c.*1485G>A		3_prime_UTR_variant	6/6		NP_001017917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB561	ENST00000360793.8	c.*1485G>A		3_prime_UTR_variant	6/6	1	NM_001915.4	ENSP00000354028.3
CYB561	ENST00000392975.6	c.*1485G>A		3_prime_UTR_variant	6/6	1		ENSP00000376701.2
CYB561	ENST00000392976.5	c.*1485G>A		3_prime_UTR_variant	6/6	3		ENSP00000376702.1
CYB561	ENST00000584031.5	c.*1703G>A		3_prime_UTR_variant	6/6	2		ENSP00000463162.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81976 AN: 151938 Hom.: 23329 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.476 AC: 272 AN: 572 Hom.: 73 Cov.: 0 AF XY: 0.456 AC XY: 145 AN XY: 318

Gnomad4 AFR exome AF: 0.813

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.619

GnomAD4 genome AF: 0.539 AC: 82023 AN: 152056 Hom.: 23340 Cov.: 32 AF XY: 0.535 AC XY: 39762 AN XY: 74328

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.491

Alfa AF: 0.490 Hom.: 18319

Bravo AF: 0.536

Asia WGS AF: 0.362 AC: 1262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
DANN	Benign	0.41

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

Other links and lift over

dbSNP: rs3087776; hg19: chr17-61510278; COSMIC: COSV105260441; COSMIC: COSV105260441;