Genetic Variant BLVRA:p.Ala35Ala (chr7-43787996-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000712.4(BLVRA):c.105G>A(p.Ala35Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,614,198 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 30 hom. )

Consequence

BLVRA
NM_000712.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.599

Publications

0 publications found

Variant links:

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)

BLVRA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 7-43787996-G-A is Benign according to our data. Variant chr7-43787996-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 2055170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.599 with no splicing effect.

BS2

High AC in GnomAd4 at 558 AD,Unknown gene.

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.105G>A	p.Ala35Ala	synonymous	Exon 3 of 8	NP_000703.2
	BLVRA	NM_001253823.2		c.105G>A	p.Ala35Ala	synonymous	Exon 4 of 9	NP_001240752.1	A0A140VJF4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BLVRA	ENST00000265523.9	TSL:1 MANE Select	c.105G>A	p.Ala35Ala	synonymous	Exon 3 of 8	ENSP00000265523.4	P53004
BLVRA	ENST00000940902.1		c.105G>A	p.Ala35Ala	synonymous	Exon 3 of 9	ENSP00000610961.1
BLVRA	ENST00000854107.1		c.105G>A	p.Ala35Ala	synonymous	Exon 3 of 8	ENSP00000524166.1

Frequencies

GnomAD3 genomes

AF:

0.00367

AC:

558

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0156

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00488

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00402

AC:

1012

AN:

251468

AF XY:

0.00398

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0180

Gnomad NFE exome

AF:

0.00415

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00466

AC:

6811

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00455

AC XY:

3312

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33480

American (AMR)

AF:

0.000604

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00199

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00286

AC:

247

AN:

86258

European-Finnish (FIN)

AF:

0.0187

AC:

1000

AN:

53420

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00470

AC:

5225

AN:

1112010

Other (OTH)

AF:

0.00394

AC:

238

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

485

971

1456

1942

2427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00366

AC:

558

AN:

152306

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

288

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000650

AC:

AN:

41568

American (AMR)

AF:

0.000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00166

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0156

AC:

165

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00488

AC:

332

AN:

68038

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00454

Hom.:

Bravo

AF:

0.00233

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00379

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.3

(source)

DANN

Benign

0.77

PhyloP100

-0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over