Genetic Variant ENST00000455220.6:c.-36T>G (chr11-83278782-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000455220.6(CCDC90B):c.-36T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CCDC90B
ENST00000455220.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.800

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19610357).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000455220.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC90B	NM_021825.5	MANE Select	c.268T>G	p.Leu90Val	missense	Exon 3 of 9	NP_068597.2
CCDC90B	NM_001286116.2		c.-36T>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 9	NP_001273045.2	Q9GZT6-3
CCDC90B	NM_001286117.3		c.-36T>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 9	NP_001273046.1	Q9GZT6-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC90B	ENST00000455220.6	TSL:1	c.-36T>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 9	ENSP00000390990.3	Q9GZT6-3
CCDC90B	ENST00000529689.6	TSL:1 MANE Select	c.268T>G	p.Leu90Val	missense	Exon 3 of 9	ENSP00000434724.1	Q9GZT6-1
CCDC90B	ENST00000455220.6	TSL:1	c.-36T>G		5_prime_UTR	Exon 3 of 9	ENSP00000390990.3	Q9GZT6-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251330

AF XY:

0.00000736

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461372

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39612

South Asian (SAS)

AF:

0.000104

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111812

Other (OTH)

AF:

0.0000331

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000824

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

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0052

Eigen

Benign

-0.034

Eigen_PC

Benign

-0.061

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.76

M_CAP

Benign

0.010

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

0.80

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.72

REVEL

Benign

0.12

Sift

Benign

0.26

Sift4G

Uncertain

0.016

Polyphen

0.98

Vest4

0.44

MutPred

0.43

Gain of helix (P = 0.1736)

MVP

0.38

MPC

0.027

ClinPred

0.45

GERP RS

1.8

PromoterAI

0.036

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.65

Mutation Taster

=61/39

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over