rs699512

Variant names:

• chr7-43771165-G-A
• rs699512
• NM_000712.4:c.7G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000712.4(BLVRA):​c.7G>A​(p.Ala3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 1,612,758 control chromosomes in the GnomAD database, including 495,414 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (52420 hom., cov: 32)
  • Exomes 𝑓: 0.78 (442994 hom.)
• Consequence: BLVRA NM_000712.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.538
• Publications: 57 publications found

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]

BLVRA Gene-Disease associations (from GenCC):

• hyperbiliverdinemia

  Inheritance: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.306974E-7).
• BP6: Variant 7-43771165-G-A is Benign according to our data. Variant chr7-43771165-G-A is described in ClinVar as Benign. ClinVar VariationId is 2118005.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLVRA	NM_000712.4	c.7G>A	p.Ala3Thr	missense_variant	Exon 2 of 8	ENST00000265523.9	NP_000703.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLVRA	ENST00000265523.9	c.7G>A	p.Ala3Thr	missense_variant	Exon 2 of 8	1	NM_000712.4	ENSP00000265523.4
BLVRA	ENST00000402924.5	c.7G>A	p.Ala3Thr	missense_variant	Exon 3 of 9	2		ENSP00000385757.1
BLVRA	ENST00000424330.1	c.7G>A	p.Ala3Thr	missense_variant	Exon 2 of 5	3		ENSP00000412005.1
BLVRA	ENST00000453612.1	n.31G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125664 AN: 152108 Hom.: 52354 Cov.: 32

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.811

GnomAD2 exomes AF: 0.801 AC: 201314 AN: 251440 AF XY: 0.799

Gnomad AFR exome AF: 0.939

Gnomad AMR exome AF: 0.877

Gnomad ASJ exome AF: 0.779

Gnomad EAS exome AF: 0.694

Gnomad FIN exome AF: 0.800

Gnomad NFE exome AF: 0.768

Gnomad OTH exome AF: 0.801

GnomAD4 exome AF: 0.777 AC: 1135417 AN: 1460532 Hom.: 442994 Cov.: 53 AF XY: 0.778 AC XY: 565512 AN XY: 726668

African (AFR) AF: 0.943 AC: 31563 AN: 33468

American (AMR) AF: 0.872 AC: 38981 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 20486 AN: 26130

East Asian (EAS) AF: 0.688 AC: 27298 AN: 39696

South Asian (SAS) AF: 0.836 AC: 72051 AN: 86228

European-Finnish (FIN) AF: 0.798 AC: 42606 AN: 53418

Middle Eastern (MID) AF: 0.839 AC: 4839 AN: 5766

European-Non Finnish (NFE) AF: 0.765 AC: 849998 AN: 1110744

Other (OTH) AF: 0.788 AC: 47595 AN: 60362

GnomAD4 genome AF: 0.826 AC: 125796 AN: 152226 Hom.: 52420 Cov.: 32 AF XY: 0.826 AC XY: 61497 AN XY: 74428

African (AFR) AF: 0.935 AC: 38845 AN: 41536

American (AMR) AF: 0.857 AC: 13118 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2751 AN: 3472

East Asian (EAS) AF: 0.690 AC: 3568 AN: 5174

South Asian (SAS) AF: 0.831 AC: 4010 AN: 4826

European-Finnish (FIN) AF: 0.803 AC: 8497 AN: 10584

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52336 AN: 68020

Other (OTH) AF: 0.812 AC: 1714 AN: 2110

Alfa AF: 0.790 Hom.: 186856

Bravo AF: 0.833

TwinsUK AF: 0.765 AC: 2837

ALSPAC AF: 0.763 AC: 2941

ESP6500AA AF: 0.927 AC: 4086

ESP6500EA AF: 0.765 AC: 6579

ExAC AF: 0.801 AC: 97244

Asia WGS AF: 0.775 AC: 2695 AN: 3478

EpiCase AF: 0.772

EpiControl AF: 0.772

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.3
DANN	Benign	0.74
DEOGEN2	Benign	0.015	T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.32	.;T;T
MetaRNN	Benign	6.3e-7	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.34	N;N;.
PhyloP100		-0.54
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.40	N;N;N
REVEL	Benign	0.044
Sift	Benign	0.54	T;T;T
Sift4G	Benign	0.99	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.022
MPC		0.19
ClinPred		0.0036	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.51
Mutation Taster		=100/0	polymorphism (auto)

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: rs699512; hg19: chr7-43810764; COSMIC: COSV55515779; COSMIC: COSV55515779;