Variant chr1-202966865-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016243.3(CYB5R1):c.49C>G(p.Leu17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

CYB5R1
NM_016243.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

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:

CYB5R1 (HGNC:):

CYB5R1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09433296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5R1	NM_016243.3 linkuse as main transcript	c.49C>G	p.Leu17Val	missense_variant	2/9	ENST00000367249.9	NP_057327.2	Q9UHQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CYB5R1	ENST00000367249.9 linkuse as main transcript	c.49C>G	p.Leu17Val	missense_variant	2/9	1	NM_016243.3	ENSP00000356218.4	Q9UHQ9
CYB5R1	ENST00000473599.5 linkuse as main transcript	n.119C>G		non_coding_transcript_exon_variant	2/5	3
CYB5R1	ENST00000478009.1 linkuse as main transcript	n.69C>G		non_coding_transcript_exon_variant	2/3	2
CYB5R1	ENST00000482572.5 linkuse as main transcript	n.87C>G		non_coding_transcript_exon_variant	2/8	5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000525

AC:

AN:

247570

Hom.:

AF XY:

0.0000745

AC XY:

AN XY:

134220

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000537

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1461098

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726820

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.49C>G (p.L17V) alteration is located in exon 2 (coding exon 2) of the CYB5R1 gene. This alteration results from a C to G substitution at nucleotide position 49, causing the leucine (L) at amino acid position 17 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.014

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.63

M_CAP

Benign

0.024

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.70

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.36

REVEL

Benign

0.18

Sift

Benign

0.70

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.10

MutPred

0.54

Loss of helix (P = 0.0093);

MVP

0.88

MPC

0.51

ClinPred

0.051

GERP RS

3.5

Varity_R

0.14

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over