dbSNP rs2232849: CYB5R1:c.646-149C>T (chr1-202963314-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 ENST00000367249.9(CYB5R1):c.646-149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00897 in 617,626 control chromosomes in the GnomAD database, including 222 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 0.025 ( 160 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 62 hom. )

Consequence

CYB5R1
ENST00000367249.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0360

Publications

5 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=-0.6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367249.9. 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.646-149C>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.646-149C>T	intron	N/A	ENSP00000356218.4
CYB5R1	ENST00000483915.1	TSL:2	n.246C>T	non_coding_transcript_exon	Exon 1 of 2
CYB5R1	ENST00000446185.1	TSL:5	c.439-149C>T	intron	N/A	ENSP00000396382.1

Frequencies

GnomAD3 genomes

AF:

0.0245

AC:

3723

AN:

152122

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0823

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.0196

GnomAD4 exome

AF:

0.00389

AC:

1810

AN:

465386

Hom.:

Cov.:

AF XY:

0.00341

AC XY:

838

AN XY:

245596

show subpopulations

African (AFR)

AF:

0.0867

AC:

1104

AN:

12728

American (AMR)

AF:

0.00836

AC:

162

AN:

19380

Ashkenazi Jewish (ASJ)

AF:

0.0103

AC:

144

AN:

13980

East Asian (EAS)

AF:

0.00

AC:

AN:

31332

South Asian (SAS)

AF:

0.000289

AC:

AN:

44954

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32544

Middle Eastern (MID)

AF:

0.00854

AC:

AN:

2224

European-Non Finnish (NFE)

AF:

0.000437

AC:

123

AN:

281622

Other (OTH)

AF:

0.00920

AC:

245

AN:

26622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

165

248

330

413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0245

AC:

3733

AN:

152240

Hom.:

160

Cov.:

AF XY:

0.0238

AC XY:

1773

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0822

AC:

3414

AN:

41516

American (AMR)

AF:

0.0125

AC:

192

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

68014

Other (OTH)

AF:

0.0198

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

178

355

533

710

888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0308

Hom.:

Bravo

AF:

0.0288

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

-0.036

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

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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