Variant 8-86939603-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173538.3(CNBD1):c.280A>G(p.Asn94Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,583,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. N94S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 0 hom. )

Consequence

CNBD1
NM_173538.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00300

Variant links:

Genes affected

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

CNBD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012260169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CNBD1	NM_173538.3 linkuse as main transcript	c.280A>G	p.Asn94Asp	missense_variant	4/11	ENST00000518476.6
CNBD1	XM_017013149.2 linkuse as main transcript	c.280A>G	p.Asn94Asp	missense_variant	4/11
CNBD1	XM_024447082.2 linkuse as main transcript	c.280A>G	p.Asn94Asp	missense_variant	4/7
CNBD1	XM_047421411.1 linkuse as main transcript	c.115A>G	p.Asn39Asp	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CNBD1	ENST00000518476.6 linkuse as main transcript	c.280A>G	p.Asn94Asp	missense_variant	4/11	1	NM_173538.3
CNBD1	ENST00000523299.6 linkuse as main transcript	c.280A>G	p.Asn94Asp	missense_variant	4/13	3		P1
CNBD1	ENST00000517748.1 linkuse as main transcript	n.334A>G		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.000723

AC:

110

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00138

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000723

AC:

162

AN:

224218

Hom.:

AF XY:

0.000770

AC XY:

AN XY:

122020

show subpopulations

Gnomad AFR exome

AF:

0.000271

Gnomad AMR exome

AF:

0.000218

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00140

Gnomad OTH exome

AF:

0.000765

GnomAD4 exome

AF:

0.00161

AC:

2311

AN:

1431148

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

1089

AN XY:

711724

show subpopulations

Gnomad4 AFR exome

AF:

0.000317

Gnomad4 AMR exome

AF:

0.000187

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.00199

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.000722

AC:

110

AN:

152274

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00138

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.000710

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00122

AC:

ExAC

AF:

0.000662

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2023

The c.280A>G (p.N94D) alteration is located in exon 4 (coding exon 4) of the CNBD1 gene. This alteration results from a A to G substitution at nucleotide position 280, causing the asparagine (N) at amino acid position 94 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.85

Cadd

Benign

1.4

Dann

Benign

0.43

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.27

M_CAP

Benign

0.0024

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.30

REVEL

Benign

0.021

Sift

Benign

0.69

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.11

MVP

0.030

MPC

0.0043

ClinPred

0.0069

GERP RS

-1.3

Varity_R

0.042

gMVP

0.077

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over