rs2232853

Positions:

• chr1-202962830-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.746-131C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,191,240 control chromosomes in the GnomAD database, including 40,985 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 0.22 (4228 hom., cov: 32)
  • Exomes 𝑓: 0.25 (36757 hom.)
• Consequence: CYB5R1 NM_016243.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5R1	NM_016243.3	c.746-131C>T		intron_variant		ENST00000367249.9	NP_057327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5R1	ENST00000367249.9	c.746-131C>T		intron_variant		1	NM_016243.3	ENSP00000356218	P1
CYB5R1	ENST00000497655.1	n.2079C>T		non_coding_transcript_exon_variant	2/2	2
CYB5R1	ENST00000482572.5	n.711-131C>T		intron_variant, non_coding_transcript_variant		5
CYB5R1	ENST00000483915.1	n.495-131C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33657 AN: 152020 Hom.: 4229 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0464

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.251 AC: 261277 AN: 1039102 Hom.: 36757 Cov.: 14 AF XY: 0.246 AC XY: 129877 AN XY: 527472

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.0367

Gnomad4 SAS exome AF: 0.0680

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.221 AC: 33655 AN: 152138 Hom.: 4228 Cov.: 32 AF XY: 0.213 AC XY: 15841 AN XY: 74376

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0459

Gnomad4 SAS AF: 0.0665

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.254

Alfa AF: 0.246 Hom.: 757

Bravo AF: 0.218

Asia WGS AF: 0.0690 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.78

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: rs2232853; hg19: chr1-202931958; COSMIC: COSV61852436; COSMIC: COSV61852436;