7-43792717-A-C

Position:

• chr7-43792717-A-C

Variant summary

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

The NM_000712.4(BLVRA):​c.257A>C​(p.Gln86Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BLVRA NM_000712.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.28

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/exons	MANE	Protein	UniProt
BLVRA	NM_000712.4	c.257A>C	p.Gln86Pro	missense_variant, splice_region_variant	5/8	ENST00000265523.9	NP_000703.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLVRA	ENST00000265523.9	c.257A>C	p.Gln86Pro	missense_variant, splice_region_variant	5/8	1	NM_000712.4	ENSP00000265523	P1
BLVRA	ENST00000402924.5	c.257A>C	p.Gln86Pro	missense_variant, splice_region_variant	6/9	2		ENSP00000385757	P1
BLVRA	ENST00000424330.1	c.257A>C	p.Gln86Pro	missense_variant, splice_region_variant	5/5	3		ENSP00000412005

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.257A>C (p.Q86P) alteration is located in exon 5 (coding exon 4) of the BLVRA gene. This alteration results from a A to C substitution at nucleotide position 257, causing the glutamine (Q) at amino acid position 86 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	Benign	0.31
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T;T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Benign	0.0057	T
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	M;M;.
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N;N;D
REVEL	Uncertain	0.30
Sift	Benign	0.16	T;T;D
Sift4G	Benign	0.27	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.70
MutPred		0.60		Gain of catalytic residue at Q86 (P = 0.0435);Gain of catalytic residue at Q86 (P = 0.0435);Gain of catalytic residue at Q86 (P = 0.0435);
MVP		0.21
MPC		0.67
ClinPred		0.93	D
GERP RS		4.2
Varity_R		0.73
gMVP		0.77

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: chr7-43832316;