dbSNP rs757502949: CYB561D1:p.Met68Thr (chr1-109494574-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000310611.8(CYB561D1):c.203T>C(p.Met68Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000332 in 1,416,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

CYB561D1
ENST00000310611.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.60

Publications

0 publications found

Variant links:

Genes affected

CYB561D1 (HGNC:26804): (cytochrome b561 family member D1) Predicted to enable heme binding activity and oxidoreductase activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CYB561D1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.043459177).

BP6

Variant 1-109494574-T-C is Benign according to our data. Variant chr1-109494574-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2259445.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYB561D1	NM_182580.3 link	c.148+287T>C		intron_variant	Intron 1 of 2	ENST00000420578.7	NP_872386.1	Q8N8Q1-1Q6ZQS1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB561D1	ENST00000420578.7 link	c.148+287T>C		intron_variant	Intron 1 of 2	1	NM_182580.3	ENSP00000413530.2		Q8N8Q1-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000272

AC:

AN:

146936

AF XY:

0.0000257

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000725

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1264706

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

621212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28342

American (AMR)

AF:

0.00

AC:

AN:

30826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20536

East Asian (EAS)

AF:

0.00

AC:

AN:

22888

South Asian (SAS)

AF:

0.0000261

AC:

AN:

76534

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36442

Middle Eastern (MID)

AF:

0.000594

AC:

AN:

5054

European-Non Finnish (NFE)

AF:

0.0000392

AC:

AN:

994356

Other (OTH)

AF:

0.0000201

AC:

AN:

49728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41546

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67998

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000388

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000377

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 09, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.9

(source)

DANN

Benign

0.74

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.33

T;T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.043

T;T;T

MetaSVM

Benign

-0.98

PhyloP100

-3.6

PrimateAI

Benign

0.44

PROVEAN

Benign

0.18

N;N;N

REVEL

Benign

0.010

Sift

Benign

0.36

T;T;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.071

MutPred

0.24

Gain of phosphorylation at M68 (P = 0.06);Gain of phosphorylation at M68 (P = 0.06);Gain of phosphorylation at M68 (P = 0.06);

MVP

0.067

MPC

0.31

ClinPred

0.065

GERP RS

-2.4

PromoterAI

-0.00060

Neutral

(source)

gMVP

0.38

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over