rs2232849

chr1-202963314-G-A

Variant summary

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

The NM_016243.3(CYB5R1):c.646-149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00897 in 617,626 control chromosomes in the GnomAD database, including 222 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 0.025 (160 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (62 hom.)
• Consequence: CYB5R1 NM_016243.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB5R1	NM_016243.3	c.646-149C>T		intron_variant		ENST00000367249.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB5R1	ENST00000367249.9	c.646-149C>T		intron_variant		1	NM_016243.3	P1

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 3723 AN: 152122 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.00389 AC: 1810 AN: 465386 Hom.: 62 Cov.: 5 AF XY: 0.00341 AC XY: 838 AN XY: 245596

Gnomad4 AFR exome AF: 0.0867

Gnomad4 AMR exome AF: 0.00836

Gnomad4 ASJ exome AF: 0.0103

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000289

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000437

Gnomad4 OTH exome AF: 0.00920

GnomAD4 genome AF: 0.0245 AC: 3733 AN: 152240 Hom.: 160 Cov.: 32 AF XY: 0.0238 AC XY: 1773 AN XY: 74444

Gnomad4 AFR AF: 0.0822

Gnomad4 AMR AF: 0.0125

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.0308 Hom.: 32

Bravo AF: 0.0288

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	13
Dann	Benign	0.80

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: rs2232849; hg19: chr1-202932442;