Genetic Variant NM_016243.3:c.746-131C>T (chr1-202962830-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016243.3(CYB5R1):c.746-131C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,191,240 control chromosomes in the GnomAD database, including 40,985 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 0.22 ( 4228 hom., cov: 32)

Exomes 𝑓: 0.25 ( 36757 hom. )

Consequence

CYB5R1
NM_016243.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

Publications

24 publications found

Variant links:

Genes affected

CYB5R1 (HGNC:13397): (cytochrome b5 reductase 1) Predicted to enable FAD binding activity. Predicted to be involved in bicarbonate transport. Located in extracellular exosome; membrane; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

CYB5R1 links:

ENSG00000307108 (HGNC:):

ENSG00000307108 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016243.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R1	NM_016243.3	MANE Select	c.746-131C>T		intron	N/A	NP_057327.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYB5R1	ENST00000367249.9	TSL:1 MANE Select	c.746-131C>T	intron	N/A	ENSP00000356218.4
CYB5R1	ENST00000497655.1	TSL:2	n.2079C>T	non_coding_transcript_exon	Exon 2 of 2
CYB5R1	ENST00000482572.5	TSL:5	n.711-131C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33657

AN:

152020

Hom.:

4229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.0464

Gnomad SAS

AF:

0.0671

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.251

AC:

261277

AN:

1039102

Hom.:

36757

Cov.:

AF XY:

0.246

AC XY:

129877

AN XY:

527472

show subpopulations

African (AFR)

AF:

0.129

AC:

3170

AN:

24484

American (AMR)

AF:

0.152

AC:

5333

AN:

35034

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

4380

AN:

22916

East Asian (EAS)

AF:

0.0367

AC:

1253

AN:

34158

South Asian (SAS)

AF:

0.0680

AC:

4933

AN:

72594

European-Finnish (FIN)

AF:

0.244

AC:

11927

AN:

48914

Middle Eastern (MID)

AF:

0.195

AC:

743

AN:

3802

European-Non Finnish (NFE)

AF:

0.291

AC:

218647

AN:

751006

Other (OTH)

AF:

0.236

AC:

10891

AN:

46194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

9673

19346

29020

38693

48366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5850

11700

17550

23400

29250

<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:

0.221

AC:

33655

AN:

152138

Hom.:

4228

Cov.:

AF XY:

0.213

AC XY:

15841

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.142

AC:

5915

AN:

41514

American (AMR)

AF:

0.194

AC:

2962

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

675

AN:

3466

East Asian (EAS)

AF:

0.0459

AC:

238

AN:

5180

South Asian (SAS)

AF:

0.0665

AC:

321

AN:

4824

European-Finnish (FIN)

AF:

0.234

AC:

2476

AN:

10590

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.299

AC:

20336

AN:

67966

Other (OTH)

AF:

0.254

AC:

534

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1299

2598

3897

5196

6495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.246

Hom.:

757

Bravo

AF:

0.218

Asia WGS

AF:

0.0690

AC:

238

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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