rs142505402

Variant names:

• chr19-40458237-C-G
• rs142505402
• NM_000713.3:c.252G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-40458237-C-G
• chr19-40458237-C-A
• chr19-40458237-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000713.3(BLVRB):​c.252G>C​(p.Thr84Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,520,548 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0074 (12 hom., cov: 31)
  • Exomes 𝑓: 0.00082 (2 hom.)
• Consequence: BLVRB NM_000713.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.645
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057838857).
• BP6: Variant 19-40458237-C-G is Benign according to our data. Variant chr19-40458237-C-G is described in ClinVar as Benign. ClinVar VariationId is 784395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.645 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00745 (1095/147014) while in subpopulation AFR AF = 0.0253 (1030/40734). AF 95% confidence interval is 0.024. There are 12 homozygotes in GnomAd4. There are 517 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 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.252G>C	p.Thr84Thr	synonymous	Exon 3 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.252G>C	p.Thr84Thr	synonymous	Exon 3 of 5	ENSP00000263368.3	P30043
	BLVRB	ENST00000643519.1		c.388G>C	p.Asp130His	missense	Exon 2 of 4	ENSP00000494515.1	A0A2R8YEP4
	BLVRB	ENST00000926837.1		c.252G>C	p.Thr84Thr	synonymous	Exon 3 of 5	ENSP00000596896.1

Frequencies

GnomAD3 genomes AF: 0.00747 AC: 1097 AN: 146888 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00316

Gnomad ASJ AF: 0.000591

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000234

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000906

Gnomad OTH AF: 0.00438

GnomAD2 exomes AF: 0.00187 AC: 463 AN: 247670 AF XY: 0.00138

Gnomad AFR exome AF: 0.0240

Gnomad AMR exome AF: 0.00157

Gnomad ASJ exome AF: 0.000802

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000144

Gnomad OTH exome AF: 0.000823

GnomAD4 exome AF: 0.000823 AC: 1131 AN: 1373534 Hom.: 2 Cov.: 32 AF XY: 0.000724 AC XY: 494 AN XY: 682482

African (AFR) AF: 0.0259 AC: 798 AN: 30870

American (AMR) AF: 0.00195 AC: 82 AN: 41952

Ashkenazi Jewish (ASJ) AF: 0.000752 AC: 17 AN: 22610

East Asian (EAS) AF: 0.00 AC: 0 AN: 31084

South Asian (SAS) AF: 0.0000821 AC: 7 AN: 85310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47866

Middle Eastern (MID) AF: 0.00133 AC: 7 AN: 5276

European-Non Finnish (NFE) AF: 0.000101 AC: 106 AN: 1053994

Other (OTH) AF: 0.00209 AC: 114 AN: 54572

GnomAD4 genome AF: 0.00745 AC: 1095 AN: 147014 Hom.: 12 Cov.: 31 AF XY: 0.00721 AC XY: 517 AN XY: 71698

African (AFR) AF: 0.0253 AC: 1030 AN: 40734

American (AMR) AF: 0.00316 AC: 47 AN: 14876

Ashkenazi Jewish (ASJ) AF: 0.000591 AC: 2 AN: 3384

East Asian (EAS) AF: 0.00 AC: 0 AN: 4628

South Asian (SAS) AF: 0.000234 AC: 1 AN: 4280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000906 AC: 6 AN: 66220

Other (OTH) AF: 0.00434 AC: 9 AN: 2076

Alfa AF: 0.000610 Hom.: 0

Bravo AF: 0.00841

ESP6500AA AF: 0.0241 AC: 106

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00232 AC: 282

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: 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	0.098
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.5
DANN	Benign	0.74
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0058	T
PhyloP100		0.65
GERP RS		-5.3
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs142505402; hg19: chr19-40964144;