7-43770671-C-T

Variant names:

• chr7-43770671-C-T
• rs699510
• NM_000712.4:c.-21-467C>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.-21-467C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,048 control chromosomes in the GnomAD database, including 52,521 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 0.83 (52521 hom., cov: 30)
• Consequence: BLVRA NM_000712.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671
• Publications: 10 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 = 0.931 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.-21-467C>T		intron	N/A	NP_000703.2
	BLVRA	NM_001253823.2		c.-21-467C>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.-21-467C>T		intron	N/A	ENSP00000265523.4
	BLVRA	ENST00000402924.5	TSL:2	c.-21-467C>T		intron	N/A	ENSP00000385757.1
	BLVRA	ENST00000424330.1	TSL:3	c.-21-467C>T		intron	N/A	ENSP00000412005.1

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125696 AN: 151930 Hom.: 52454 Cov.: 30

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.828 AC: 125829 AN: 152048 Hom.: 52521 Cov.: 30 AF XY: 0.828 AC XY: 61509 AN XY: 74328

African (AFR) AF: 0.939 AC: 38942 AN: 41468

American (AMR) AF: 0.858 AC: 13109 AN: 15278

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

East Asian (EAS) AF: 0.690 AC: 3567 AN: 5168

South Asian (SAS) AF: 0.832 AC: 3996 AN: 4804

European-Finnish (FIN) AF: 0.804 AC: 8492 AN: 10568

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

European-Non Finnish (NFE) AF: 0.769 AC: 52301 AN: 67978

Other (OTH) AF: 0.813 AC: 1712 AN: 2106

Alfa AF: 0.817 Hom.: 9981

Bravo AF: 0.835

Asia WGS AF: 0.775 AC: 2697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.72
PhyloP100		-0.67
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: rs699510; hg19: chr7-43810270;