Variant 16-69424687-T-G 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_030579.3(CYB5B):c.4T>G(p.Ser2Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,574,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CYB5B
NM_030579.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.389

Variant links:

Genes affected

CYB5B (HGNC:24374): (cytochrome b5 type B) Enables heme binding activity. Contributes to nitrite reductase (NO-forming) activity. Involved in nitric oxide biosynthetic process. Located in membrane. Part of nitric-oxide synthase complex. [provided by Alliance of Genome Resources, Apr 2022]

CYB5B links:

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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=0.20470053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5B	NM_030579.3 linkuse as main transcript	c.4T>G	p.Ser2Ala	missense_variant	1/5	ENST00000307892.13	NP_085056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5B	ENST00000307892.13 linkuse as main transcript	c.4T>G	p.Ser2Ala	missense_variant	1/5	1	NM_030579.3	ENSP00000308430	P2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152074

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000916

AC:

AN:

218312

Hom.:

AF XY:

0.00000843

AC XY:

AN XY:

118684

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000199

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000105

AC:

AN:

1422562

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

705978

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000137

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74274

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.0000165

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 14, 2023

The c.4T>G (p.S2A) alteration is located in exon 1 (coding exon 1) of the CYB5B gene. This alteration results from a T to G substitution at nucleotide position 4, causing the serine (S) at amino acid position 2 to be replaced by an alanine (A). 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

0.071

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.8

DANN

Benign

0.59

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.30

M_CAP

Benign

0.030

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.52

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.020

REVEL

Benign

0.094

Sift

Uncertain

0.028

Sift4G

Benign

0.34

Vest4

0.18

MVP

0.69

MPC

0.13

ClinPred

0.12

GERP RS

-5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.27

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over