Variant 1-202966783-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.097 ( 1324 hom., cov: 31)

Exomes 𝑓: 0.059 ( 7287 hom. )

Consequence

CYB5R1
NM_016243.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.890

Variant links:

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]

CYB5R1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5R1	NM_016243.3 linkuse as main transcript	c.131A>G	p.Asn44Ser	missense_variant	2/9	ENST00000367249.9	NP_057327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CYB5R1	ENST00000367249.9 linkuse as main transcript	c.131A>G	p.Asn44Ser	missense_variant	2/9	1	NM_016243.3	ENSP00000356218	P1
CYB5R1	ENST00000473599.5 linkuse as main transcript	n.201A>G		non_coding_transcript_exon_variant	2/5	3
CYB5R1	ENST00000478009.1 linkuse as main transcript	n.151A>G		non_coding_transcript_exon_variant	2/3	2
CYB5R1	ENST00000482572.5 linkuse as main transcript	n.169A>G		non_coding_transcript_exon_variant	2/8	5

Frequencies

GnomAD3 genomes

AF:

0.0964

AC:

14660

AN:

152060

Hom.:

1308

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.115

AC:

28863

AN:

251196

Hom.:

3484

AF XY:

0.107

AC XY:

14569

AN XY:

135794

show subpopulations

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 SAS exome

AF:

0.149

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.:

AF XY:

0.0604

AC XY:

43946

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.146

Gnomad4 AMR exome

AF:

0.226

Gnomad4 ASJ exome

AF:

0.0173

Gnomad4 EAS exome

AF:

0.431

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.0782

Gnomad4 NFE exome

AF:

0.0292

Gnomad4 OTH exome

AF:

0.0710

GnomAD4 genome

AF:

0.0967

AC:

14712

AN:

152178

Hom.:

1324

Cov.:

AF XY:

0.103

AC XY:

7665

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.0205

Gnomad4 EAS

AF:

0.432

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.0785

Gnomad4 NFE

AF:

0.0302

Gnomad4 OTH

AF:

0.0926

Alfa

AF:

0.0516

Hom.:

1407

Bravo

AF:

0.105

TwinsUK

AF:

0.0267

AC:

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.019

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.27

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

REVEL

Benign

0.19

Sift

Benign

0.57

Sift4G

Benign

0.62

Polyphen

0.0010

Vest4

0.14

MPC

0.080

ClinPred

0.00069

GERP RS

3.4

Varity_R

0.041

gMVP

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over