rs2232844

Positions:

• chr1-202964739-A-G

Variant summary

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

The NM_016243.3(CYB5R1):​c.476-44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,397,146 control chromosomes in the GnomAD database, including 278 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 0.024 (148 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (130 hom.)
• Consequence: CYB5R1 NM_016243.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

Genes affected

CYB5R1 (HGNC:13397): (cytochrome b5 reductase 1) Predicted to enable FAD binding activity. Predicted to be involved in bicarbonate transport. Located in extracellular exosome; membrane; and mitochondrion. [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 (AFR) allele frequency at 95% confidence interval = 0.0808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB5R1	NM_016243.3	c.476-44T>C		intron_variant		ENST00000367249.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB5R1	ENST00000367249.9	c.476-44T>C		intron_variant		1	NM_016243.3	P1
CYB5R1	ENST00000446185.1	c.271-44T>C		intron_variant		5
CYB5R1	ENST00000497655.1	n.646T>C		non_coding_transcript_exon_variant	1/2	2
CYB5R1	ENST00000482572.5	n.441-44T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3635 AN: 152220 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0831

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00955

GnomAD3 exomes AF: 0.00629 AC: 1577 AN: 250592 Hom.: 67 AF XY: 0.00449 AC XY: 609 AN XY: 135534

Gnomad AFR exome AF: 0.0863

Gnomad AMR exome AF: 0.00391

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00253 AC: 3151 AN: 1244808 Hom.: 130 Cov.: 18 AF XY: 0.00211 AC XY: 1328 AN XY: 630196

Gnomad4 AFR exome AF: 0.0860

Gnomad4 AMR exome AF: 0.00484

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000330

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000799

Gnomad4 OTH exome AF: 0.00602

GnomAD4 genome AF: 0.0239 AC: 3647 AN: 152338 Hom.: 148 Cov.: 32 AF XY: 0.0229 AC XY: 1709 AN XY: 74496

Gnomad4 AFR AF: 0.0831

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.00945

Alfa AF: 0.0220 Hom.: 15

Bravo AF: 0.0281

Asia WGS AF: 0.00635 AC: 22 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	4.4
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2232844; hg19: chr1-202933867;