Variant chr1-54174681-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001031672.4(CYB5RL):c.886A>G(p.Lys296Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000345 in 1,613,624 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 2 hom. )

Consequence

CYB5RL
NM_001031672.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.02

Variant links:

Genes affected

CYB5RL (HGNC:32220): (cytochrome b5 reductase like) Predicted to enable cytochrome-b5 reductase activity, acting on NAD(P)H. Predicted to be involved in bicarbonate transport. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CYB5RL links:

ENSG00000256407 (HGNC:):

ENSG00000256407 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5RL	NM_001031672.4 link	c.886A>G	p.Lys296Glu	missense_variant	8/8	ENST00000534324.6	NP_001026842.2	Q6IPT4-1
CYB5RL	NM_001353353.2 link	c.649A>G	p.Lys217Glu	missense_variant	6/6		NP_001340282.1
CYB5RL	NM_001353354.2 link	c.442A>G	p.Lys148Glu	missense_variant	7/7		NP_001340283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5RL	ENST00000534324.6 link	c.886A>G	p.Lys296Glu	missense_variant	8/8	5	NM_001031672.4	ENSP00000434343.1		Q6IPT4-1
ENSG00000256407	ENST00000637610.1 link	n.303+9480A>G		intron_variant		5		ENSP00000490901.1		A0A1B0GWF0

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000177

AC:

AN:

248368

Hom.:

AF XY:

0.000223

AC XY:

AN XY:

134752

show subpopulations

Gnomad AFR exome

AF:

0.0000650

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000373

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000360

AC:

526

AN:

1461294

Hom.:

Cov.:

AF XY:

0.000378

AC XY:

275

AN XY:

726878

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000434

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.000204

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000412

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000479

AC:

ExAC

AF:

0.000166

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000534

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 02, 2021

The c.886A>G (p.K296E) alteration is located in exon 8 (coding exon 6) of the CYB5RL gene. This alteration results from a A to G substitution at nucleotide position 886, causing the lysine (K) at amino acid position 296 to be replaced by a glutamic acid (E). 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

0.062

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.085

DANN

Benign

0.63

DEOGEN2

Benign

0.038

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

-0.030

.;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.30

N;N

REVEL

Benign

0.094

Sift

Benign

0.60

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.025

.;B

Vest4

0.15

MVP

0.085

ClinPred

0.040

GERP RS

-5.0

Varity_R

0.062

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.22

Position offset: -13

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