Variant 19-40458237-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000713.3(BLVRB):c.252G>C(p.Thr84Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,520,548 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 12 hom., cov: 31)

Exomes 𝑓: 0.00082 ( 2 hom. )

Consequence

BLVRB
NM_000713.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.645

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057838857).

BP6

Variant 19-40458237-C-G is Benign according to our data. Variant chr19-40458237-C-G is described in ClinVar as [Benign]. Clinvar id is 784395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.645 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00745 (1095/147014) while in subpopulation AFR AF= 0.0253 (1030/40734). AF 95% confidence interval is 0.024. There are 12 homozygotes in gnomad4. There are 517 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLVRB	NM_000713.3 linkuse as main transcript	c.252G>C	p.Thr84Thr	synonymous_variant	3/5	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.252G>C	p.Thr84Thr	synonymous_variant	3/5	1	NM_000713.3	ENSP00000263368.3		P30043

Frequencies

GnomAD3 genomes

AF:

0.00747

AC:

1097

AN:

146888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00316

Gnomad ASJ

AF:

0.000591

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000234

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000906

Gnomad OTH

AF:

0.00438

GnomAD3 exomes

AF:

0.00187

AC:

463

AN:

247670

Hom.:

AF XY:

0.00138

AC XY:

185

AN XY:

134138

show subpopulations

Gnomad AFR exome

AF:

0.0240

Gnomad AMR exome

AF:

0.00157

Gnomad ASJ exome

AF:

0.000802

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000144

Gnomad OTH exome

AF:

0.000823

GnomAD4 exome

AF:

0.000823

AC:

1131

AN:

1373534

Hom.:

Cov.:

AF XY:

0.000724

AC XY:

494

AN XY:

682482

show subpopulations

Gnomad4 AFR exome

AF:

0.0259

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.000752

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000821

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.00209

GnomAD4 genome

AF:

0.00745

AC:

1095

AN:

147014

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

517

AN XY:

71698

show subpopulations

Gnomad4 AFR

AF:

0.0253

Gnomad4 AMR

AF:

0.00316

Gnomad4 ASJ

AF:

0.000591

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000234

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000906

Gnomad4 OTH

AF:

0.00434

Alfa

AF:

0.000610

Hom.:

Bravo

AF:

0.00841

ESP6500AA

AF:

0.0241

AC:

106

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00232

AC:

282

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.5

DANN

Benign

0.74

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0058

GERP RS

-5.3

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

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