chr7-43787944-G-C

Variant names:

• chr7-43787944-G-C
• rs763832285
• NM_000712.4:c.53G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000712.4(BLVRA):​c.53G>C​(p.Arg18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BLVRA NM_000712.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25

Genes affected

BLVRA (HGNC:1062): (biliverdin reductase A) The protein encoded by this gene belongs to the biliverdin reductase family, members of which catalyze the conversion of biliverdin to bilirubin in the presence of NADPH or NADH. Mutations in this gene are associated with hyperbiliverdinemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLVRA	NM_000712.4	c.53G>C	p.Arg18Pro	missense_variant	Exon 3 of 8	ENST00000265523.9	NP_000703.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLVRA	ENST00000265523.9	c.53G>C	p.Arg18Pro	missense_variant	Exon 3 of 8	1	NM_000712.4	ENSP00000265523.4
BLVRA	ENST00000402924.5	c.53G>C	p.Arg18Pro	missense_variant	Exon 4 of 9	2		ENSP00000385757.1
BLVRA	ENST00000424330.1	c.53G>C	p.Arg18Pro	missense_variant	Exon 3 of 5	3		ENSP00000412005.1
BLVRA	ENST00000453612.1	n.77G>C		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251448 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135904

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000221 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.53G>C (p.R18P) alteration is located in exon 3 (coding exon 2) of the BLVRA gene. This alteration results from a G to C substitution at nucleotide position 53, causing the arginine (R) at amino acid position 18 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	0.0098	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.94	.;D;D
M_CAP	Benign	0.0031	T
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.6	N;N;D
REVEL	Benign	0.27
Sift	Benign	0.24	T;T;D
Sift4G	Benign	0.27	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.58
MutPred		0.72		Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);
MVP		0.30
MPC		0.86
ClinPred		0.98	D
GERP RS		5.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.95
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs763832285; hg19: chr7-43827543;