rs10234057

Variant names:

• chr7-43771221-C-T
• rs10234057
• NM_000712.4:c.12+51C>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.12+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,589,976 control chromosomes in the GnomAD database, including 30,046 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 0.15 (2208 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27838 hom.)
• Consequence: BLVRA NM_000712.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 11 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, AR, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLVRA	NM_000712.4	MANE Select	c.12+51C>T		intron	N/A	NP_000703.2
	BLVRA	NM_001253823.2		c.12+51C>T		intron	N/A	NP_001240752.1	A0A140VJF4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLVRA	ENST00000265523.9	TSL:1 MANE Select	c.12+51C>T		intron	N/A	ENSP00000265523.4	P53004
	BLVRA	ENST00000940902.1		c.12+51C>T		intron	N/A	ENSP00000610961.1
	BLVRA	ENST00000854107.1		c.12+51C>T		intron	N/A	ENSP00000524166.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23131 AN: 152028 Hom.: 2208 Cov.: 32

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.00791

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.152

GnomAD2 exomes AF: 0.158 AC: 39740 AN: 250872 AF XY: 0.164

Gnomad AFR exome AF: 0.0591

Gnomad AMR exome AF: 0.0924

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.00887

Gnomad FIN exome AF: 0.226

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.182

GnomAD4 exome AF: 0.190 AC: 273230 AN: 1437830 Hom.: 27838 Cov.: 29 AF XY: 0.189 AC XY: 135746 AN XY: 716798

African (AFR) AF: 0.0560 AC: 1845 AN: 32954

American (AMR) AF: 0.0965 AC: 4310 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 4727 AN: 25952

East Asian (EAS) AF: 0.00467 AC: 185 AN: 39612

South Asian (SAS) AF: 0.125 AC: 10686 AN: 85714

European-Finnish (FIN) AF: 0.219 AC: 11680 AN: 53392

Middle Eastern (MID) AF: 0.186 AC: 1061 AN: 5718

European-Non Finnish (NFE) AF: 0.210 AC: 228523 AN: 1090226

Other (OTH) AF: 0.171 AC: 10213 AN: 59608

GnomAD4 genome AF: 0.152 AC: 23126 AN: 152146 Hom.: 2208 Cov.: 32 AF XY: 0.149 AC XY: 11070 AN XY: 74366

African (AFR) AF: 0.0625 AC: 2595 AN: 41528

American (AMR) AF: 0.130 AC: 1986 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 630 AN: 3472

East Asian (EAS) AF: 0.00792 AC: 41 AN: 5174

South Asian (SAS) AF: 0.115 AC: 554 AN: 4820

European-Finnish (FIN) AF: 0.226 AC: 2391 AN: 10558

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14514 AN: 67988

Other (OTH) AF: 0.150 AC: 317 AN: 2110

Alfa AF: 0.169 Hom.: 618

Bravo AF: 0.141

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.30
PhyloP100		-0.26
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: rs10234057; hg19: chr7-43810820;