19-40451399-C-A

Variant names:

• chr19-40451399-C-A
• rs113166043
• NM_000713.3:c.428G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000713.3(BLVRB):​c.428G>T​(p.Gly143Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G143D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BLVRB NM_000713.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.833

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.428G>T	p.Gly143Val	missense	Exon 4 of 5	NP_000704.1	P30043

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLVRB	ENST00000263368.9	TSL:1 MANE Select	c.428G>T	p.Gly143Val	missense	Exon 4 of 5	ENSP00000263368.3	P30043
	BLVRB	ENST00000643519.1		c.545G>T	p.Gly182Val	missense	Exon 3 of 4	ENSP00000494515.1	A0A2R8YEP4
	BLVRB	ENST00000926837.1		c.428G>T	p.Gly143Val	missense	Exon 4 of 5	ENSP00000596896.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.023	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		4.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.74		Loss of helix (P = 0.0795)
MVP		0.86
MPC		0.85
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.87
gMVP		0.79
Mutation Taster		=41/59	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs113166043; hg19: chr19-40957306;