2-171553387-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000375252.3(CYBRD1):c.235G>A(p.Ala79Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,613,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

CYBRD1
ENST00000375252.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0610

Variant links:

Genes affected

CYBRD1 (HGNC:20797): (cytochrome b reductase 1) This gene is a member of the cytochrome b(561) family that encodes an iron-regulated protein. It highly expressed in the duodenal brush border membrane. It has ferric reductase activity and is believed to play a physiological role in dietary iron absorption. [provided by RefSeq, Jul 2008]

CYBRD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009544402).

BP6

Variant 2-171553387-G-A is Benign according to our data. Variant chr2-171553387-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3079297.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CYBRD1	NM_024843.4 linkuse as main transcript	c.444G>A	p.Pro148=	synonymous_variant	3/4	ENST00000321348.9
CYBRD1	NM_001127383.2 linkuse as main transcript	c.235G>A	p.Ala79Thr	missense_variant	2/3
CYBRD1	NM_001256909.2 linkuse as main transcript	c.270G>A	p.Pro90=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYBRD1	ENST00000375252.3 linkuse as main transcript	c.235G>A	p.Ala79Thr	missense_variant	2/3	1			Q53TN4-2
CYBRD1	ENST00000321348.9 linkuse as main transcript	c.444G>A	p.Pro148=	synonymous_variant	3/4	1	NM_024843.4	P1	Q53TN4-1
CYBRD1	ENST00000409484.5 linkuse as main transcript	c.270G>A	p.Pro90=	synonymous_variant	3/4	2			Q53TN4-3
CYBRD1	ENST00000445146.1 linkuse as main transcript	c.327G>A	p.Pro109=	synonymous_variant	3/4	3

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000147

AC:

AN:

251016

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000125

AC:

182

AN:

1461316

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

114

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.000823

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000756

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000237

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000789

Hom.:

Bravo

AF:

0.000212

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000181

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.31

Cadd

Benign

Dann

Benign

0.95

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.38

M_CAP

Benign

0.0022

MetaRNN

Benign

0.0095

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;N

PROVEAN

Benign

0.10

REVEL

Benign

0.030

Sift

Benign

0.59

Sift4G

Benign

0.15

Polyphen

0.0040

Vest4

0.094

MVP

0.12

ClinPred

0.010

GERP RS

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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