19-40451463-G-C

Variant names:

• chr19-40451463-G-C
• NM_000713.3:c.364C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000713.3(BLVRB):​c.364C>G​(p.Pro122Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,130 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P122S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BLVRB NM_000713.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.41

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.911

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLVRB	NM_000713.3	c.364C>G	p.Pro122Ala	missense_variant	Exon 4 of 5	ENST00000263368.9	NP_000704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLVRB	ENST00000263368.9	c.364C>G	p.Pro122Ala	missense_variant	Exon 4 of 5	1	NM_000713.3	ENSP00000263368.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461130 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726792

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	.;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.9	.;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-6.7	.;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0080	.;D
Sift4G	Uncertain	0.023	.;D
Polyphen		1.0	.;D
Vest4		0.56
MutPred		0.81		.;Loss of catalytic residue at P122 (P = 0.047);
MVP		0.51
MPC		0.65
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.66
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-40957370;