rs145609085

Variant names:

• chr19-40451409-G-C
• rs145609085
• NM_000713.3:c.418C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-40451409-G-C
• chr19-40451409-G-A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong 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. 14/22 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.31
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -16 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 VariationId is 709797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000713.3. 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
	BLVRB	NM_000713.3	MANE Select	c.418C>G	p.Arg140Gly	missense	Exon 4 of 5	NP_000704.1	P30043

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLVRB	ENST00000263368.9	TSL:1 MANE Select	c.418C>G	p.Arg140Gly	missense	Exon 4 of 5	ENSP00000263368.3	P30043
	BLVRB	ENST00000643519.1		c.535C>G	p.Arg179Gly	missense	Exon 3 of 4	ENSP00000494515.1	A0A2R8YEP4
	BLVRB	ENST00000926837.1		c.418C>G	p.Arg140Gly	missense	Exon 4 of 5	ENSP00000596896.1

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

GnomAD2 exomes AF: 0.00178 AC: 438 AN: 245688 AF XY: 0.00174

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 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

African (AFR) AF: 0.000628 AC: 21 AN: 33456

American (AMR) AF: 0.00189 AC: 84 AN: 44334

Ashkenazi Jewish (ASJ) AF: 0.0000769 AC: 2 AN: 26002

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39642

South Asian (SAS) AF: 0.000983 AC: 84 AN: 85476

European-Finnish (FIN) AF: 0.000244 AC: 13 AN: 53242

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5764

European-Non Finnish (NFE) AF: 0.00362 AC: 4017 AN: 1111076

Other (OTH) AF: 0.00283 AC: 171 AN: 60320

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

African (AFR) AF: 0.000746 AC: 31 AN: 41562

American (AMR) AF: 0.00229 AC: 35 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00323 AC: 220 AN: 68014

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.0099	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		2.3
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.063
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.089	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
Mutation Taster		=90/10	polymorphism

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