chr3-50350952-C-A

Position:

• chr3-50350952-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001291284.2(CYB561D2):​c.-58C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 1,329,492 control chromosomes in the GnomAD database, including 7,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.088 (1924 hom., cov: 33)
  • Exomes 𝑓: 0.023 (5199 hom.)
• Consequence: CYB561D2 NM_001291284.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.202

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-50350952-C-A is Benign according to our data. Variant chr3-50350952-C-A is described in ClinVar as [Benign]. Clinvar id is 1289666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB561D2	NM_001291284.2	c.-58C>A		5_prime_UTR_variant	1/4	ENST00000425346.6
LOC127898564	NR_183066.1	n.91C>A		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB561D2	ENST00000425346.6	c.-58C>A		5_prime_UTR_variant	1/4	1	NM_001291284.2	P1

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 13335 AN: 152188 Hom.: 1923 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0469

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00348

Gnomad OTH AF: 0.0788

GnomAD4 exome AF: 0.0232 AC: 27356 AN: 1177186 Hom.: 5199 Cov.: 18 AF XY: 0.0221 AC XY: 12561 AN XY: 567314

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.00472

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.00994

Gnomad4 FIN exome AF: 0.0448

Gnomad4 NFE exome AF: 0.00136

Gnomad4 OTH exome AF: 0.0503

GnomAD4 genome AF: 0.0877 AC: 13360 AN: 152306 Hom.: 1924 Cov.: 33 AF XY: 0.0941 AC XY: 7008 AN XY: 74464

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0469

Gnomad4 NFE AF: 0.00348

Gnomad4 OTH AF: 0.0794

Alfa AF: 0.0244 Hom.: 401

Bravo AF: 0.110

Asia WGS AF: 0.203 AC: 704 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2233476; hg19: chr3-50388383;