1-202966783-T-C

Variant names:

• chr1-202966783-T-C
• rs2232842
• NM_016243.3:c.131A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016243.3(CYB5R1):​c.131A>G​(p.Asn44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 1,613,964 control chromosomes in the GnomAD database, including 8,611 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.097 (1324 hom., cov: 31)
  • Exomes 𝑓: 0.059 (7287 hom.)
• Consequence: CYB5R1 NM_016243.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890
• Publications: 21 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020075738).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016243.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R1	NM_016243.3	MANE Select	c.131A>G	p.Asn44Ser	missense	Exon 2 of 9	NP_057327.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R1	ENST00000367249.9	TSL:1 MANE Select	c.131A>G	p.Asn44Ser	missense	Exon 2 of 9	ENSP00000356218.4	Q9UHQ9
	CYB5R1	ENST00000893436.1		c.131A>G	p.Asn44Ser	missense	Exon 2 of 9	ENSP00000563495.1
	CYB5R1	ENST00000964627.1		c.131A>G	p.Asn44Ser	missense	Exon 2 of 9	ENSP00000634686.1

Frequencies

GnomAD3 genomes AF: 0.0964 AC: 14660 AN: 152060 Hom.: 1308 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0859

GnomAD2 exomes AF: 0.115 AC: 28863 AN: 251196 AF XY: 0.107

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.0171

Gnomad EAS exome AF: 0.435

Gnomad FIN exome AF: 0.0823

Gnomad NFE exome AF: 0.0297

Gnomad OTH exome AF: 0.0847

GnomAD4 exome AF: 0.0591 AC: 86368 AN: 1461786 Hom.: 7287 Cov.: 32 AF XY: 0.0604 AC XY: 43946 AN XY: 727208

African (AFR) AF: 0.146 AC: 4875 AN: 33478

American (AMR) AF: 0.226 AC: 10085 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 453 AN: 26120

East Asian (EAS) AF: 0.431 AC: 17107 AN: 39698

South Asian (SAS) AF: 0.147 AC: 12668 AN: 86256

European-Finnish (FIN) AF: 0.0782 AC: 4174 AN: 53410

Middle Eastern (MID) AF: 0.0373 AC: 215 AN: 5768

European-Non Finnish (NFE) AF: 0.0292 AC: 32501 AN: 1111946

Other (OTH) AF: 0.0710 AC: 4290 AN: 60396

GnomAD4 genome AF: 0.0967 AC: 14712 AN: 152178 Hom.: 1324 Cov.: 31 AF XY: 0.103 AC XY: 7665 AN XY: 74410

African (AFR) AF: 0.148 AC: 6157 AN: 41510

American (AMR) AF: 0.155 AC: 2366 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2226 AN: 5154

South Asian (SAS) AF: 0.163 AC: 789 AN: 4828

European-Finnish (FIN) AF: 0.0785 AC: 833 AN: 10608

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0302 AC: 2055 AN: 68006

Other (OTH) AF: 0.0926 AC: 195 AN: 2106

Alfa AF: 0.0576 Hom.: 2994

Bravo AF: 0.105

TwinsUK AF: 0.0267 AC: 99

ALSPAC AF: 0.0262 AC: 101

ESP6500AA AF: 0.147 AC: 648

ESP6500EA AF: 0.0276 AC: 237

ExAC AF: 0.109 AC: 13198

Asia WGS AF: 0.283 AC: 981 AN: 3478

EpiCase AF: 0.0276

EpiControl AF: 0.0244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.75
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.89
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.19
Sift	Benign	0.57	T
Sift4G	Benign	0.62	T
Polyphen		0.0010	B
Vest4		0.14
MPC		0.080
ClinPred		0.00069	T
GERP RS		3.4
PromoterAI		-0.029	Neutral
Varity_R		0.041
gMVP		0.52
Mutation Taster		=92/8	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: rs2232842; hg19: chr1-202935911; COSMIC: COSV65916810; COSMIC: COSV65916810;