3-50351176-C-A

Position:

• chr3-50351176-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001291284.2(CYB561D2):​c.-26+192C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 522,946 control chromosomes in the GnomAD database, including 22,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (10859 hom., cov: 33)
  • Exomes 𝑓: 0.20 (11167 hom.)
• Consequence: CYB561D2 NM_001291284.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.65

Genes affected

CYB561D2 (HGNC:30253): (cytochrome b561 family member D2) Enables heme binding activity and transmembrane monodehydroascorbate reductase activity. Involved in ascorbate homeostasis. Predicted to be located in vesicle. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

LOC127898564 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-50351176-C-A is Benign according to our data. Variant chr3-50351176-C-A is described in ClinVar as [Benign]. Clinvar id is 1231684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB561D2	NM_001291284.2	c.-26+192C>A		intron_variant		ENST00000425346.6	NP_001278213.1
LOC127898564	NR_183066.1	n.123+192C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB561D2	ENST00000425346.6	c.-26+192C>A		intron_variant		1	NM_001291284.2	ENSP00000400454	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47928 AN: 152086 Hom.: 10814 Cov.: 33

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.200 AC: 74030 AN: 370742 Hom.: 11167 Cov.: 5 AF XY: 0.196 AC XY: 37466 AN XY: 191586

Gnomad4 AFR exome AF: 0.594

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.585

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.316 AC: 48036 AN: 152204 Hom.: 10859 Cov.: 33 AF XY: 0.319 AC XY: 23718 AN XY: 74420

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.297

Alfa AF: 0.177 Hom.: 3134

Bravo AF: 0.351

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.11
DANN	Benign	0.80

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: rs2233474; hg19: chr3-50388607;