19-40458478-G-T

Variant names:

• chr19-40458478-G-T
• rs747352017
• NM_000713.3:c.147C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000713.3(BLVRB):​c.147C>A​(p.His49Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,822 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. 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. H49D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BLVRB NM_000713.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1593518).

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.147C>A	p.His49Gln	missense	Exon 2 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.147C>A	p.His49Gln	missense	Exon 2 of 5	ENSP00000263368.3	P30043
	BLVRB	ENST00000643519.1		c.147C>A	p.His49Gln	missense	Exon 2 of 4	ENSP00000494515.1	A0A2R8YEP4
	BLVRB	ENST00000926837.1		c.147C>A	p.His49Gln	missense	Exon 2 of 5	ENSP00000596896.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456822 Hom.: 0 Cov.: 35 AF XY: 0.00000276 AC XY: 2 AN XY: 724322

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26006

East Asian (EAS) AF: 0.00 AC: 0 AN: 39528

South Asian (SAS) AF: 0.00 AC: 0 AN: 85158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110236

Other (OTH) AF: 0.00 AC: 0 AN: 60138

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.1
DANN	Benign	0.80
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.10	N
PhyloP100		-0.57
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.75	N
REVEL	Benign	0.064
Sift	Benign	0.28	T
Sift4G	Benign	0.46	T
Polyphen		0.0020	B
Vest4		0.20
MutPred		0.31		Loss of sheet (P = 0.0817)
MVP		0.35
MPC		0.20
ClinPred		0.097	T
GERP RS		-3.0
Varity_R		0.14
gMVP		0.25
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs747352017; hg19: chr19-40964385;