19-40451409-G-C

Position:

• chr19-40451409-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000713.3(BLVRB):​c.418C>G​(p.Arg140Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,611,586 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (7 hom.)
• Consequence: BLVRB NM_000713.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.31

Genes affected

BLVRB (HGNC:1063): (biliverdin reductase B) Enables biliverdin reductase (NAD(P)+) activity and riboflavin reductase (NADPH) activity. Involved in heme catabolic process. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009909898).
• BP6: Variant 19-40451409-G-C is Benign according to our data. Variant chr19-40451409-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 709797.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLVRB	NM_000713.3	c.418C>G	p.Arg140Gly	missense_variant	4/5	ENST00000263368.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLVRB	ENST00000263368.9	c.418C>G	p.Arg140Gly	missense_variant	4/5	1	NM_000713.3	P1

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 293 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00323

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00178 AC: 438 AN: 245688 Hom.: 2 AF XY: 0.00174 AC XY: 231 AN XY: 132758

Gnomad AFR exome AF: 0.000698

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000909

Gnomad FIN exome AF: 0.000380

Gnomad NFE exome AF: 0.00292

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00301 AC: 4398 AN: 1459312 Hom.: 7 Cov.: 30 AF XY: 0.00299 AC XY: 2171 AN XY: 725598

Gnomad4 AFR exome AF: 0.000628

Gnomad4 AMR exome AF: 0.00189

Gnomad4 ASJ exome AF: 0.0000769

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000983

Gnomad4 FIN exome AF: 0.000244

Gnomad4 NFE exome AF: 0.00362

Gnomad4 OTH exome AF: 0.00283

GnomAD4 genome AF: 0.00192 AC: 293 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.00176 AC XY: 131 AN XY: 74446

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00323

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00234 Hom.: 2

Bravo AF: 0.00211

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00419 AC: 36

ExAC AF: 0.00159 AC: 193

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.35	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.0099	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
Polyphen		0.0080	.;B
Vest4		0.25
MVP		0.37
MPC		0.26
ClinPred		0.021	T
GERP RS		1.8
Varity_R		0.41
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs145609085; hg19: chr19-40957316; COSMIC: COSV99647825; COSMIC: COSV99647825;