11-61359386-C-T

Position:

• chr11-61359386-C-T

Variant summary

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

The NM_153611.6(CYB561A3):​c.-111-1558G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,052 control chromosomes in the GnomAD database, including 45,598 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 0.74 (45588 hom., cov: 30)
  • Exomes 𝑓: 0.95 (10 hom.)
• Consequence: CYB561A3 NM_153611.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

Genes affected

CYB561A3 (HGNC:23014): (cytochrome b561 family member A3) Predicted to enable transmembrane ascorbate ferrireductase activity. Predicted to be involved in cellular iron ion homeostasis. Located in nucleolus. [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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB561A3	NM_153611.6	c.-111-1558G>A		intron_variant		ENST00000294072.9	NP_705839.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB561A3	ENST00000294072.9	c.-111-1558G>A		intron_variant		1	NM_153611.6	ENSP00000294072	P1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113113 AN: 151912 Hom.: 45588 Cov.: 30

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.793

GnomAD4 exome AF: 0.955 AC: 21 AN: 22 Hom.: 10 Cov.: 0 AF XY: 0.944 AC XY: 17 AN XY: 18

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.744 AC: 113129 AN: 152030 Hom.: 45588 Cov.: 30 AF XY: 0.750 AC XY: 55729 AN XY: 74332

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.870

Gnomad4 OTH AF: 0.788

Alfa AF: 0.854 Hom.: 90334

Bravo AF: 0.727

Asia WGS AF: 0.830 AC: 2884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.60

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: rs4939517; hg19: chr11-61126858;