Variant 2-171554604-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000321348.9(CYBRD1):c.638C>A(p.Ala213Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CYBRD1
ENST00000321348.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CYBRD1	NM_024843.4 linkuse as main transcript	c.638C>A	p.Ala213Asp	missense_variant	4/4	ENST00000321348.9	NP_079119.3
CYBRD1	NM_001256909.2 linkuse as main transcript	c.464C>A	p.Ala155Asp	missense_variant	4/4		NP_001243838.1
CYBRD1	NM_001127383.2 linkuse as main transcript	c.429C>A	p.Gly143=	synonymous_variant	3/3		NP_001120855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBRD1	ENST00000321348.9 linkuse as main transcript	c.638C>A	p.Ala213Asp	missense_variant	4/4	1	NM_024843.4	ENSP00000319141	P1	Q53TN4-1
CYBRD1	ENST00000375252.3 linkuse as main transcript	c.429C>A	p.Gly143=	synonymous_variant	3/3	1		ENSP00000364401		Q53TN4-2
CYBRD1	ENST00000409484.5 linkuse as main transcript	c.464C>A	p.Ala155Asp	missense_variant	4/4	2		ENSP00000386739		Q53TN4-3
CYBRD1	ENST00000445146.1 linkuse as main transcript	c.521C>A	p.Ala174Asp	missense_variant	4/4	3		ENSP00000402242

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727178

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 27, 2021

The c.638C>A (p.A213D) alteration is located in exon 4 (coding exon 4) of the CYBRD1 gene. This alteration results from a C to A substitution at nucleotide position 638, causing the alanine (A) at amino acid position 213 to be replaced by an aspartic acid (D). 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

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

.;D;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.67

D;D;D

MetaSVM

Benign

-0.41

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.028

D;D;D

Sift4G

Uncertain

0.030

D;D;D

Polyphen

0.96

.;D;.

Vest4

0.75

MutPred

0.65

.;Gain of sheet (P = 0.0827);.;

MVP

0.75

MPC

1.3

ClinPred

0.99

GERP RS

5.0

Varity_R

0.72

gMVP

0.92

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over