Variant 7-43787944-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000712.4(BLVRA):c.53G>C(p.Arg18Pro) 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 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BLVRA
NM_000712.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25

Variant links:

Genes affected

BLVRA (HGNC:1062): (biliverdin reductase A) The protein encoded by this gene belongs to the biliverdin reductase family, members of which catalyze the conversion of biliverdin to bilirubin in the presence of NADPH or NADH. Mutations in this gene are associated with hyperbiliverdinemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2011]

BLVRA links:

BLVRA (HGNC:):

BLVRA 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	UniProt
BLVRA	NM_000712.4 linkuse as main transcript	c.53G>C	p.Arg18Pro	missense_variant	3/8	ENST00000265523.9	NP_000703.2	P53004A0A140VJF4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BLVRA	ENST00000265523.9 linkuse as main transcript	c.53G>C	p.Arg18Pro	missense_variant	3/8	1	NM_000712.4	ENSP00000265523.4	P53004
BLVRA	ENST00000402924.5 linkuse as main transcript	c.53G>C	p.Arg18Pro	missense_variant	4/9	2		ENSP00000385757.1	P53004
BLVRA	ENST00000424330.1 linkuse as main transcript	c.53G>C	p.Arg18Pro	missense_variant	3/5	3		ENSP00000412005.1	C9J1E1
BLVRA	ENST00000453612.1 linkuse as main transcript	n.77G>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251448

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000221

Hom.:

Bravo

AF:

0.0000151

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 21, 2024

The c.53G>C (p.R18P) alteration is located in exon 3 (coding exon 2) of the BLVRA gene. This alteration results from a G to C substitution at nucleotide position 53, causing the arginine (R) at amino acid position 18 to be replaced by a proline (P). 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

0.89

BayesDel_addAF

Benign

0.0098

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

T;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.94

.;D;D

M_CAP

Benign

0.0031

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.5

M;M;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.6

N;N;D

REVEL

Benign

0.27

Sift

Benign

0.24

T;T;D

Sift4G

Benign

0.27

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.58

MutPred

0.72

Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);

MVP

0.30

MPC

0.86

ClinPred

0.98

GERP RS

5.1

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.95

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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