Genetic Variant CYB5RL:c.*2875C>T (chr1-54171744-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_001031672.4(CYB5RL):c.*2875C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 320,352 control chromosomes in the GnomAD database, including 76,768 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 0.66 ( 33903 hom., cov: 31)

Exomes 𝑓: 0.71 ( 42865 hom. )

Consequence

CYB5RL
NM_001031672.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.553

Publications

4 publications found

Variant links:

Genes affected

CYB5RL (HGNC:32220): (cytochrome b5 reductase like) Predicted to enable cytochrome-b5 reductase activity, acting on NAD(P)H. Predicted to be involved in bicarbonate transport. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CYB5RL links:

ENSG00000256407 (HGNC:):

ENSG00000256407 links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031672.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYB5RL	NM_001031672.4	MANE Select	c.*2875C>T	3_prime_UTR	Exon 8 of 8	NP_001026842.2
CYB5RL	NM_001353353.2		c.*2875C>T	3_prime_UTR	Exon 6 of 6	NP_001340282.1
CYB5RL	NM_001353354.2		c.*2875C>T	3_prime_UTR	Exon 7 of 7	NP_001340283.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYB5RL	ENST00000534324.6	TSL:5 MANE Select	c.*2875C>T	3_prime_UTR	Exon 8 of 8	ENSP00000434343.1
ENSG00000256407	ENST00000637610.1	TSL:5	n.303+12417C>T	intron	N/A	ENSP00000490901.1
CYB5RL	ENST00000287899.13	TSL:3	c.*2875C>T	3_prime_UTR	Exon 5 of 5	ENSP00000287899.8

Frequencies

GnomAD3 genomes

AF:

0.658

AC:

99845

AN:

151804

Hom.:

33884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.474

Gnomad AMI

AF:

0.682

Gnomad AMR

AF:

0.667

Gnomad ASJ

AF:

0.742

Gnomad EAS

AF:

0.730

Gnomad SAS

AF:

0.653

Gnomad FIN

AF:

0.771

Gnomad MID

AF:

0.640

Gnomad NFE

AF:

0.740

Gnomad OTH

AF:

0.668

GnomAD4 exome

AF:

0.709

AC:

119413

AN:

168430

Hom.:

42865

Cov.:

AF XY:

0.704

AC XY:

63517

AN XY:

90232

show subpopulations

African (AFR)

AF:

0.455

AC:

2263

AN:

4974

American (AMR)

AF:

0.694

AC:

7205

AN:

10388

Ashkenazi Jewish (ASJ)

AF:

0.729

AC:

2869

AN:

3938

East Asian (EAS)

AF:

0.722

AC:

5856

AN:

8112

South Asian (SAS)

AF:

0.650

AC:

20286

AN:

31204

European-Finnish (FIN)

AF:

0.765

AC:

5680

AN:

7428

Middle Eastern (MID)

AF:

0.644

AC:

375

AN:

582

European-Non Finnish (NFE)

AF:

0.738

AC:

68846

AN:

93350

Other (OTH)

AF:

0.714

AC:

6033

AN:

8454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1636

3271

4907

6542

8178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.658

AC:

99906

AN:

151922

Hom.:

33903

Cov.:

AF XY:

0.657

AC XY:

48772

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.474

AC:

19604

AN:

41366

American (AMR)

AF:

0.667

AC:

10187

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.742

AC:

2572

AN:

3466

East Asian (EAS)

AF:

0.729

AC:

3749

AN:

5140

South Asian (SAS)

AF:

0.653

AC:

3141

AN:

4812

European-Finnish (FIN)

AF:

0.771

AC:

8146

AN:

10566

Middle Eastern (MID)

AF:

0.647

AC:

189

AN:

292

European-Non Finnish (NFE)

AF:

0.740

AC:

50287

AN:

67984

Other (OTH)

AF:

0.669

AC:

1412

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1650

3301

4951

6602

8252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.678

Hom.:

5418

Bravo

AF:

0.642

Asia WGS

AF:

0.645

AC:

2241

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

(source)

DANN

Benign

0.69

PhyloP100

0.55

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

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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