Genetic Variant CYB561A3:c.-111-1558G>A (chr11-61359386-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_153611.6(CYB561A3):c.-111-1558G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,052 control chromosomes in the GnomAD database, including 45,598 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 0.74 ( 45588 hom., cov: 30)

Exomes 𝑓: 0.95 ( 10 hom. )

Consequence

CYB561A3
NM_153611.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.242

Publications

6 publications found

Variant links:

Genes affected

CYB561A3 (HGNC:23014): (cytochrome b561 family member A3) Predicted to enable transmembrane ascorbate ferrireductase activity. Predicted to be involved in cellular iron ion homeostasis. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

CYB561A3 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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153611.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYB561A3	NM_153611.6	MANE Select	c.-111-1558G>A	intron	N/A	NP_705839.3
CYB561A3	NM_001300763.2		c.-111-1558G>A	intron	N/A	NP_001287692.1	F5H1Q2
CYB561A3	NM_001161454.1		c.-229-1558G>A	intron	N/A	NP_001154926.1	Q8NBI2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYB561A3	ENST00000294072.9	TSL:1 MANE Select	c.-111-1558G>A	intron	N/A	ENSP00000294072.4	Q8NBI2-1
CYB561A3	ENST00000540755.5	TSL:1	n.-111-1558G>A	intron	N/A	ENSP00000445561.1	F5H240
CYB561A3	ENST00000537364.5	TSL:2	c.-1669G>A	5_prime_UTR	Exon 1 of 4	ENSP00000438725.1	F5H0P5

Frequencies

GnomAD3 genomes

AF:

0.745

AC:

113113

AN:

151912

Hom.:

45588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.916

Gnomad AMR

AF:

0.851

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.965

Gnomad SAS

AF:

0.834

Gnomad FIN

AF:

0.896

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.870

Gnomad OTH

AF:

0.793

GnomAD4 exome

AF:

0.955

AC:

AN:

Hom.:

Cov.:

AF XY:

0.944

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.875

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.825

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.744

AC:

113129

AN:

152030

Hom.:

45588

Cov.:

AF XY:

0.750

AC XY:

55729

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.401

AC:

16590

AN:

41388

American (AMR)

AF:

0.852

AC:

13006

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

3137

AN:

3472

East Asian (EAS)

AF:

0.965

AC:

5002

AN:

5184

South Asian (SAS)

AF:

0.835

AC:

4016

AN:

4810

European-Finnish (FIN)

AF:

0.896

AC:

9486

AN:

10584

Middle Eastern (MID)

AF:

0.867

AC:

255

AN:

294

European-Non Finnish (NFE)

AF:

0.870

AC:

59139

AN:

68002

Other (OTH)

AF:

0.788

AC:

1663

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1082

2164

3247

4329

5411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

822

1644

2466

3288

4110

<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:

0.831

Hom.:

209999

Bravo

AF:

0.727

Asia WGS

AF:

0.830

AC:

2884

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.3

(source)

DANN

Benign

0.60

PhyloP100

0.24

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