rs2690381

Variant names:

• chr7-43803185-C-T
• rs2690381
• NM_000712.4:c.461-491C>T

Variant summary

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

The NM_000712.4(BLVRA):​c.461-491C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,152 control chromosomes in the GnomAD database, including 5,514 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 0.24 (5514 hom., cov: 33)
• Consequence: BLVRA NM_000712.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000712.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLVRA	NM_000712.4	MANE Select	c.461-491C>T		intron	N/A	NP_000703.2
	BLVRA	NM_001253823.2		c.461-491C>T		intron	N/A	NP_001240752.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLVRA	ENST00000265523.9	TSL:1 MANE Select	c.461-491C>T		intron	N/A	ENSP00000265523.4
	BLVRA	ENST00000402924.5	TSL:2	c.461-491C>T		intron	N/A	ENSP00000385757.1
	BLVRA	ENST00000486984.1	TSL:2	n.165-491C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36869 AN: 152034 Hom.: 5516 Cov.: 33

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.242 AC: 36865 AN: 152152 Hom.: 5514 Cov.: 33 AF XY: 0.246 AC XY: 18284 AN XY: 74376

African (AFR) AF: 0.0579 AC: 2406 AN: 41526

American (AMR) AF: 0.295 AC: 4505 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1241 AN: 3472

East Asian (EAS) AF: 0.348 AC: 1800 AN: 5178

South Asian (SAS) AF: 0.437 AC: 2105 AN: 4814

European-Finnish (FIN) AF: 0.280 AC: 2954 AN: 10562

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20903 AN: 67988

Other (OTH) AF: 0.265 AC: 559 AN: 2112

Alfa AF: 0.287 Hom.: 2526

Bravo AF: 0.234

Asia WGS AF: 0.357 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.56
DANN	Benign	0.33
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: rs2690381; hg19: chr7-43842784;