Variant chr19-40451409-G-C 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.418C>G(p.Arg140Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,611,586 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 7 hom. )

Consequence

BLVRB
NM_000713.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.31

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=0.009909898).

BP6

Variant 19-40451409-G-C is Benign according to our data. Variant chr19-40451409-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 709797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLVRB	NM_000713.3 linkuse as main transcript	c.418C>G	p.Arg140Gly	missense_variant	4/5	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.418C>G	p.Arg140Gly	missense_variant	4/5	1	NM_000713.3	ENSP00000263368.3		P30043

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

293

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

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:

0.00323

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00178

AC:

438

AN:

245688

Hom.:

AF XY:

0.00174

AC XY:

231

AN XY:

132758

show subpopulations

Gnomad AFR exome

AF:

0.000698

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000909

Gnomad FIN exome

AF:

0.000380

Gnomad NFE exome

AF:

0.00292

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.00301

AC:

4398

AN:

1459312

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

2171

AN XY:

725598

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.00189

Gnomad4 ASJ exome

AF:

0.0000769

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000983

Gnomad4 FIN exome

AF:

0.000244

Gnomad4 NFE exome

AF:

0.00362

Gnomad4 OTH exome

AF:

0.00283

GnomAD4 genome

AF:

0.00192

AC:

293

AN:

152274

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00323

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00234

Hom.:

Bravo

AF:

0.00211

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00159

AC:

193

Asia WGS

AF:

0.000577

AC:

AN:

3478

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 20, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.35

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0099

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;M

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.6

.;D

REVEL

Benign

0.063

Sift

Uncertain

0.0040

.;D

Sift4G

Benign

0.089

.;T

Polyphen

0.0080

.;B

Vest4

0.25

MVP

0.37

MPC

0.26

ClinPred

0.021

GERP RS

1.8

Varity_R

0.41

gMVP

0.41

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