Genetic Variant BLVRB:p.Thr84Thr (chr19-40458237-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP7

The NM_000713.3(BLVRB):c.252G>A(p.Thr84Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,520,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T84T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

BLVRB
NM_000713.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.645

Publications

0 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 -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09942019).

BP7

Synonymous conserved (PhyloP=0.645 with no splicing effect.

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.252G>A	p.Thr84Thr	synonymous	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.252G>A	p.Thr84Thr	synonymous	Exon 3 of 5	ENSP00000263368.3	P30043
BLVRB	ENST00000643519.1		c.388G>A	p.Asp130Asn	missense	Exon 2 of 4	ENSP00000494515.1	A0A2R8YEP4
BLVRB	ENST00000926837.1		c.252G>A	p.Thr84Thr	synonymous	Exon 3 of 5	ENSP00000596896.1

Frequencies

GnomAD3 genomes

AF:

0.0000204

AC:

AN:

146890

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000234

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000323

AC:

AN:

247670

AF XY:

0.0000373

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1373546

Hom.:

Cov.:

AF XY:

0.0000484

AC XY:

AN XY:

682482

show subpopulations

African (AFR)

AF:

0.000194

AC:

AN:

30878

American (AMR)

AF:

0.0000238

AC:

AN:

41954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22610

East Asian (EAS)

AF:

0.00

AC:

AN:

31084

South Asian (SAS)

AF:

0.000117

AC:

AN:

85310

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47866

Middle Eastern (MID)

AF:

0.000569

AC:

AN:

5276

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

1053994

Other (OTH)

AF:

0.000147

AC:

AN:

54574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.0000204

AC:

AN:

147016

Hom.:

Cov.:

AF XY:

0.0000418

AC XY:

AN XY:

71700

show subpopulations

African (AFR)

AF:

0.0000245

AC:

AN:

40736

American (AMR)

AF:

0.00

AC:

AN:

14876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3384

East Asian (EAS)

AF:

0.00

AC:

AN:

4628

South Asian (SAS)

AF:

0.000234

AC:

AN:

4280

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66220

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

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:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_noAF

Benign

-0.31

CADD

Benign

8.6

(source)

DANN

Benign

0.87

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.30

MetaRNN

Benign

0.099

PhyloP100

0.65

GERP RS

-5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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