rs916321

Positions:

• chr22-42645385-G-A
• chr22-42645385-G-T

Variant summary

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

The NM_000398.7(CYB5R3):​c.21+3910C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,092 control chromosomes in the GnomAD database, including 8,565 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 0.32 (8565 hom., cov: 32)
• Consequence: CYB5R3 NM_000398.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

Genes affected

CYB5R3 (HGNC:2873): (cytochrome b5 reductase 3) This gene encodes cytochrome b5 reductase, which includes a membrane-bound form in somatic cells (anchored in the endoplasmic reticulum, mitochondrial and other membranes) and a soluble form in erythrocytes. The membrane-bound form exists mainly on the cytoplasmic side of the endoplasmic reticulum and functions in desaturation and elongation of fatty acids, in cholesterol biosynthesis, and in drug metabolism. The erythrocyte form is located in a soluble fraction of circulating erythrocytes and is involved in methemoglobin reduction. The membrane-bound form has both membrane-binding and catalytic domains, while the soluble form has only the catalytic domain. Alternate splicing results in multiple transcript variants. Mutations in this gene cause methemoglobinemias. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5R3	NM_000398.7	c.21+3910C>T		intron_variant		ENST00000352397.10	NP_000389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5R3	ENST00000352397.10	c.21+3910C>T		intron_variant		1	NM_000398.7	ENSP00000338461	P3

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48694 AN: 151974 Hom.: 8550 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.320 AC: 48730 AN: 152092 Hom.: 8565 Cov.: 32 AF XY: 0.325 AC XY: 24139 AN XY: 74336

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.315

Alfa AF: 0.344 Hom.: 3426

Bravo AF: 0.312

Asia WGS AF: 0.360 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.16
DANN	Benign	0.88

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: rs916321; hg19: chr22-43041391;