rs2232853

Variant names:

• chr1-202962830-G-A
• rs2232853
• NM_016243.3:c.746-131C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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]

ENSG00000307108 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYB5R1	NM_016243.3	c.746-131C>T		intron_variant	Intron 8 of 8	ENST00000367249.9	NP_057327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB5R1	ENST00000367249.9	c.746-131C>T		intron_variant	Intron 8 of 8	1	NM_016243.3	ENSP00000356218.4

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

African (AFR) AF: 0.129 AC: 3170 AN: 24484

American (AMR) AF: 0.152 AC: 5333 AN: 35034

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4380 AN: 22916

East Asian (EAS) AF: 0.0367 AC: 1253 AN: 34158

South Asian (SAS) AF: 0.0680 AC: 4933 AN: 72594

European-Finnish (FIN) AF: 0.244 AC: 11927 AN: 48914

Middle Eastern (MID) AF: 0.195 AC: 743 AN: 3802

European-Non Finnish (NFE) AF: 0.291 AC: 218647 AN: 751006

Other (OTH) AF: 0.236 AC: 10891 AN: 46194

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

African (AFR) AF: 0.142 AC: 5915 AN: 41514

American (AMR) AF: 0.194 AC: 2962 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3466

East Asian (EAS) AF: 0.0459 AC: 238 AN: 5180

South Asian (SAS) AF: 0.0665 AC: 321 AN: 4824

European-Finnish (FIN) AF: 0.234 AC: 2476 AN: 10590

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20336 AN: 67966

Other (OTH) AF: 0.254 AC: 534 AN: 2106

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
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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