Genetic Variant CNBD1:p.Thr149Met (chr8-87206007-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173538.3(CNBD1):c.446C>T(p.Thr149Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000491 in 1,526,824 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: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

CNBD1
NM_173538.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.200

Publications

1 publications found

Variant links:

Genes affected

CNBD1 (HGNC:26663): (cyclic nucleotide binding domain containing 1)

CNBD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13111082).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173538.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNBD1	NM_173538.3	MANE Select	c.446C>T	p.Thr149Met	missense	Exon 5 of 11	NP_775809.1	Q8NA66

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNBD1	ENST00000518476.6	TSL:1 MANE Select	c.446C>T	p.Thr149Met	missense	Exon 5 of 11	ENSP00000430073.1	Q8NA66
CNBD1	ENST00000523299.6	TSL:3	c.446C>T	p.Thr149Met	missense	Exon 5 of 13	ENSP00000430986.2	H0YC59
CNBD1	ENST00000522427.1	TSL:4	n.189C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.000194

AC:

AN:

149162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000672

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000463

AC:

AN:

172808

AF XY:

0.0000213

show subpopulations

Gnomad AFR exome

AF:

0.000485

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:

0.0000247

Gnomad OTH exome

AF:

0.000247

GnomAD4 exome

AF:

0.0000334

AC:

AN:

1377662

Hom.:

Cov.:

AF XY:

0.0000205

AC XY:

AN XY:

682622

show subpopulations

African (AFR)

AF:

0.000650

AC:

AN:

29236

American (AMR)

AF:

0.0000325

AC:

AN:

30786

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23706

East Asian (EAS)

AF:

0.0000555

AC:

AN:

36018

South Asian (SAS)

AF:

0.00

AC:

AN:

73004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49290

Middle Eastern (MID)

AF:

0.000184

AC:

AN:

5440

European-Non Finnish (NFE)

AF:

0.0000177

AC:

AN:

1073430

Other (OTH)

AF:

0.0000705

AC:

AN:

56752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

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:

0.000194

AC:

AN:

149162

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

AN XY:

72564

show subpopulations

African (AFR)

AF:

0.000672

AC:

AN:

40180

American (AMR)

AF:

0.00

AC:

AN:

15000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.000194

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9666

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67664

Other (OTH)

AF:

0.00

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0000566

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.000825

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000249

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

0.16

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.062

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.54

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.13

MetaSVM

Uncertain

0.36

MutationAssessor

Benign

0.81

PhyloP100

0.20

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.38

Sift

Benign

0.068

Sift4G

Uncertain

0.0050

Polyphen

0.99

Vest4

0.30

MVP

0.34

MPC

0.0081

ClinPred

0.12

GERP RS

4.1

PromoterAI

0.0094

Neutral

(source)

Varity_R

0.033

gMVP

0.31

Mutation Taster

=85/15

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over