Genetic Variant BLVRB:p.Arg92Gln (chr19-40458214-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_000713.3(BLVRB):c.275G>A(p.Arg92Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,601,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R92W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

BLVRB
NM_000713.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.597

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13837379).

BP6

Variant 19-40458214-C-T is Benign according to our data. Variant chr19-40458214-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3134444.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000713.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLVRB	NM_000713.3	MANE Select	c.275G>A	p.Arg92Gln	missense	Exon 3 of 5	NP_000704.1	P30043

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BLVRB	ENST00000263368.9	TSL:1 MANE Select	c.275G>A	p.Arg92Gln	missense	Exon 3 of 5	ENSP00000263368.3	P30043
BLVRB	ENST00000926837.1		c.275G>A	p.Arg92Gln	missense	Exon 3 of 5	ENSP00000596896.1
BLVRB	ENST00000858750.1		c.263G>A	p.Arg88Gln	missense	Exon 3 of 5	ENSP00000528809.1

Frequencies

GnomAD3 genomes

AF:

0.000193

AC:

AN:

150338

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000979

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000386

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000164

AC:

AN:

249490

AF XY:

0.000178

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000930

Gnomad NFE exome

AF:

0.000267

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000196

AC:

285

AN:

1450854

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

147

AN XY:

721570

show subpopulations

African (AFR)

AF:

0.0000904

AC:

AN:

33184

American (AMR)

AF:

0.0000903

AC:

AN:

44306

Ashkenazi Jewish (ASJ)

AF:

0.000429

AC:

AN:

25658

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38760

South Asian (SAS)

AF:

0.00

AC:

AN:

86066

European-Finnish (FIN)

AF:

0.0000756

AC:

AN:

52904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.000227

AC:

251

AN:

1104658

Other (OTH)

AF:

0.000185

AC:

AN:

59594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000193

AC:

AN:

150462

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

AN XY:

73552

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41302

American (AMR)

AF:

0.0000660

AC:

AN:

15148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3430

East Asian (EAS)

AF:

0.00

AC:

AN:

5004

South Asian (SAS)

AF:

0.00

AC:

AN:

4684

European-Finnish (FIN)

AF:

0.0000979

AC:

AN:

10210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000386

AC:

AN:

67394

Other (OTH)

AF:

0.00

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000250

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.81

M_CAP

Benign

0.0047

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

0.60

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.63

REVEL

Benign

0.095

Sift

Benign

0.26

Sift4G

Benign

0.47

Polyphen

0.0050

Vest4

0.34

MVP

0.24

MPC

0.23

ClinPred

0.039

GERP RS

-1.6

Varity_R

0.091

gMVP

0.49

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over