Genetic Variant NM_021825.5:c.482G>A (chr11-83273851-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021825.5(CCDC90B):c.482G>A(p.Arg161Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,608,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R161G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

CCDC90B
NM_021825.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.76

Publications

1 publications found

Variant links:

Genes affected

CCDC90B (HGNC:28108): (coiled-coil domain containing 90B) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

CCDC90B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033059955).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021825.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CCDC90B	NM_021825.5	MANE Select	c.482G>A	p.Arg161Gln	missense	Exon 6 of 9	NP_068597.2
CCDC90B	NM_001286118.3		c.188G>A	p.Arg63Gln	missense	Exon 5 of 8	NP_001273047.1
CCDC90B	NM_001286119.3		c.188G>A	p.Arg63Gln	missense	Exon 6 of 9	NP_001273048.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC90B	ENST00000529689.6	TSL:1 MANE Select	c.482G>A	p.Arg161Gln	missense	Exon 6 of 9	ENSP00000434724.1	Q9GZT6-1
CCDC90B	ENST00000455220.6	TSL:1	c.179G>A	p.Arg60Gln	missense	Exon 6 of 9	ENSP00000390990.3	Q9GZT6-3
CCDC90B	ENST00000525503.5	TSL:1	n.*670G>A		non_coding_transcript_exon	Exon 6 of 9	ENSP00000431424.2	E9PSG6

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151886

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:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000614

AC:

AN:

244164

AF XY:

0.0000530

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000596

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000498

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000364

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1456256

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

724086

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33258

American (AMR)

AF:

0.0000453

AC:

AN:

44124

Ashkenazi Jewish (ASJ)

AF:

0.0000386

AC:

AN:

25936

East Asian (EAS)

AF:

0.000253

AC:

AN:

39496

South Asian (SAS)

AF:

0.00

AC:

AN:

85352

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1109108

Other (OTH)

AF:

0.0000166

AC:

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

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:

0.0000197

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41380

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000989

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.017

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.85

M_CAP

Benign

0.0094

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.23

PhyloP100

2.8

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

REVEL

Benign

0.031

Sift

Benign

0.13

Sift4G

Benign

0.12

Polyphen

0.021

Vest4

0.31

MVP

0.37

MPC

0.029

ClinPred

0.073

GERP RS

4.2

Varity_R

0.066

gMVP

0.38

Mutation Taster

=89/11

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over