Variant 19-40458488-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000713.3(BLVRB):c.137G>A(p.Arg46Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00686 in 1,610,566 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0040 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0072 ( 36 hom. )

Consequence

BLVRB
NM_000713.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

BLVRB (HGNC:1063): (biliverdin reductase B) Enables biliverdin reductase (NAD(P)+) activity and riboflavin reductase (NADPH) activity. Involved in heme catabolic process. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

BLVRB links:

BLVRB (HGNC:):

BLVRB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060637295).

BP6

Variant 19-40458488-C-T is Benign according to our data. Variant chr19-40458488-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 709682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLVRB	NM_000713.3 linkuse as main transcript	c.137G>A	p.Arg46Gln	missense_variant	2/5	ENST00000263368.9	NP_000704.1	P30043V9HWI1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLVRB	ENST00000263368.9 linkuse as main transcript	c.137G>A	p.Arg46Gln	missense_variant	2/5	1	NM_000713.3	ENSP00000263368.3		P30043

Frequencies

GnomAD3 genomes

AF:

0.00403

AC:

613

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00716

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00392

AC:

937

AN:

238888

Hom.:

AF XY:

0.00390

AC XY:

507

AN XY:

130036

show subpopulations

Gnomad AFR exome

AF:

0.000925

Gnomad AMR exome

AF:

0.00175

Gnomad ASJ exome

AF:

0.00687

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000337

Gnomad FIN exome

AF:

0.00171

Gnomad NFE exome

AF:

0.00692

Gnomad OTH exome

AF:

0.00379

GnomAD4 exome

AF:

0.00715

AC:

10434

AN:

1458282

Hom.:

Cov.:

AF XY:

0.00688

AC XY:

4992

AN XY:

725130

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00653

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000468

Gnomad4 FIN exome

AF:

0.00196

Gnomad4 NFE exome

AF:

0.00863

Gnomad4 OTH exome

AF:

0.00741

GnomAD4 genome

AF:

0.00403

AC:

613

AN:

152284

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

247

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00716

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00686

Hom.:

Bravo

AF:

0.00425

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00826

AC:

ExAC

AF:

0.00373

AC:

452

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.0069

.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.17

T;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

.;.;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

1.2

.;.;N

REVEL

Benign

0.037

Sift

Benign

0.69

.;.;T

Sift4G

Benign

0.68

.;T;T

Polyphen

0.0

.;.;B

Vest4

0.14, 0.12

MVP

0.21

MPC

0.22

ClinPred

0.0045

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.055

gMVP

0.14

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