rs8190404

Positions:

• chr22-42644801-C-T

Variant summary

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

The NM_000398.7(CYB5R3):​c.21+4494G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,188 control chromosomes in the GnomAD database, including 1,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1731 hom., cov: 33)
• Consequence: CYB5R3 NM_000398.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.191

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 22-42644801-C-T is Benign according to our data. Variant chr22-42644801-C-T is described in ClinVar as [Benign]. Clinvar id is 1274008.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5R3	NM_000398.7	c.21+4494G>A		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+4494G>A		intron_variant		1	NM_000398.7	ENSP00000338461	P3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22261 AN: 152070 Hom.: 1725 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.147 AC: 22296 AN: 152188 Hom.: 1731 Cov.: 33 AF XY: 0.142 AC XY: 10587 AN XY: 74400

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0378

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.168

Alfa AF: 0.154 Hom.: 526

Bravo AF: 0.150

Asia WGS AF: 0.0430 AC: 156 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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.66

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: rs8190404; hg19: chr22-43040807;