2-171541683-A-G

Variant summary

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

The NM_024843.4(CYBRD1):ā€‹c.292A>Gā€‹(p.Ile98Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,782 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 (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

CYBRD1
NM_024843.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44
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]

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=0.12513277).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYBRD1NM_024843.4 linkuse as main transcriptc.292A>G p.Ile98Val missense_variant 2/4 ENST00000321348.9 NP_079119.3
CYBRD1NM_001256909.2 linkuse as main transcriptc.118A>G p.Ile40Val missense_variant 2/4 NP_001243838.1
CYBRD1NM_001127383.2 linkuse as main transcriptc.194-11663A>G intron_variant NP_001120855.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYBRD1ENST00000321348.9 linkuse as main transcriptc.292A>G p.Ile98Val missense_variant 2/41 NM_024843.4 ENSP00000319141 P1Q53TN4-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461782
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
727206
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:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsDec 21, 2023The c.292A>G (p.I98V) alteration is located in exon 2 (coding exon 2) of the CYBRD1 gene. This alteration results from a A to G substitution at nucleotide position 292, causing the isoleucine (I) at amino acid position 98 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
0.081
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
2.2
DANN
Benign
0.69
DEOGEN2
Benign
0.072
.;T;.
Eigen
Benign
-0.99
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.65
T;T;T
M_CAP
Benign
0.085
D
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.39
.;N;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.020
N;N;N
REVEL
Benign
0.053
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0020
.;B;.
Vest4
0.18
MutPred
0.66
.;Gain of catalytic residue at I98 (P = 0.0616);.;
MVP
0.55
MPC
0.34
ClinPred
0.14
T
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-172398193; API