chr7-43801810-G-C

Variant names:

• chr7-43801810-G-C
• rs2877262
• NM_000712.4:c.460+1238G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000712.4(BLVRA):​c.460+1238G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,810 control chromosomes in the GnomAD database, including 15,443 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (15443 hom., cov: 31)
• Consequence: BLVRA NM_000712.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLVRA	NM_000712.4	c.460+1238G>C		intron_variant	Intron 6 of 7	ENST00000265523.9	NP_000703.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLVRA	ENST00000265523.9	c.460+1238G>C		intron_variant	Intron 6 of 7	1	NM_000712.4	ENSP00000265523.4
BLVRA	ENST00000402924.5	c.460+1238G>C		intron_variant	Intron 7 of 8	2		ENSP00000385757.1
BLVRA	ENST00000486984.1	n.164+1238G>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67136 AN: 151690 Hom.: 15430 Cov.: 31

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.435

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.443 AC: 67195 AN: 151810 Hom.: 15443 Cov.: 31 AF XY: 0.443 AC XY: 32870 AN XY: 74170

African (AFR) AF: 0.580 AC: 24030 AN: 41408

American (AMR) AF: 0.394 AC: 6012 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3468

East Asian (EAS) AF: 0.410 AC: 2112 AN: 5154

South Asian (SAS) AF: 0.542 AC: 2607 AN: 4808

European-Finnish (FIN) AF: 0.384 AC: 4041 AN: 10514

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25335 AN: 67906

Other (OTH) AF: 0.434 AC: 914 AN: 2106

Alfa AF: 0.414 Hom.: 1646

Bravo AF: 0.446

Asia WGS AF: 0.470 AC: 1635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.68
PhyloP100		-0.52
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: rs2877262; hg19: chr7-43841409;