chr7-43796765-A-G

Variant names:

• chr7-43796765-A-G
• rs10268054
• NM_000712.4:c.353-3700A>G

Variant summary

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

The NM_000712.4(BLVRA):​c.353-3700A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,266 control chromosomes in the GnomAD database, including 2,208 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)
• Consequence: BLVRA NM_000712.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLVRA	NM_000712.4	c.353-3700A>G		intron_variant	Intron 5 of 7	ENST00000265523.9	NP_000703.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLVRA	ENST00000265523.9	c.353-3700A>G		intron_variant	Intron 5 of 7	1	NM_000712.4	ENSP00000265523.4
BLVRA	ENST00000402924.5	c.353-3700A>G		intron_variant	Intron 6 of 8	2		ENSP00000385757.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22320 AN: 152148 Hom.: 2208 Cov.: 32

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.00787

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.147 AC: 22310 AN: 152266 Hom.: 2208 Cov.: 32 AF XY: 0.143 AC XY: 10650 AN XY: 74446

African (AFR) AF: 0.0382 AC: 1587 AN: 41584

American (AMR) AF: 0.129 AC: 1979 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3468

East Asian (EAS) AF: 0.00789 AC: 41 AN: 5196

South Asian (SAS) AF: 0.116 AC: 560 AN: 4830

European-Finnish (FIN) AF: 0.226 AC: 2393 AN: 10582

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14712 AN: 67988

Other (OTH) AF: 0.148 AC: 312 AN: 2112

Alfa AF: 0.169 Hom.: 403

Bravo AF: 0.134

Asia WGS AF: 0.0610 AC: 214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.40
PhyloP100		0.19
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: rs10268054; hg19: chr7-43836364;