Variant 8-86939619-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.296A>G(p.Glu99Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,594,622 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 (★).

Frequency

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

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CNBD1
NM_173538.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

Variant links:

Genes affected

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

CNBD1 links:

CNBD1 (HGNC:):

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=0.06736484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNBD1	NM_173538.3 linkuse as main transcript	c.296A>G	p.Glu99Gly	missense_variant	4/11	ENST00000518476.6	NP_775809.1	Q8NA66
CNBD1	XM_017013149.2 linkuse as main transcript	c.296A>G	p.Glu99Gly	missense_variant	4/11		XP_016868638.1
CNBD1	XM_024447082.2 linkuse as main transcript	c.296A>G	p.Glu99Gly	missense_variant	4/7		XP_024302850.1
CNBD1	XM_047421411.1 linkuse as main transcript	c.131A>G	p.Glu44Gly	missense_variant	3/7		XP_047277367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CNBD1	ENST00000518476.6 linkuse as main transcript	c.296A>G	p.Glu99Gly	missense_variant	4/11	1	NM_173538.3	ENSP00000430073.1	Q8NA66
CNBD1	ENST00000523299.6 linkuse as main transcript	c.296A>G	p.Glu99Gly	missense_variant	4/13	3		ENSP00000430986.2	H0YC59
CNBD1	ENST00000517748.1 linkuse as main transcript	n.350A>G		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152178

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000257

AC:

AN:

233288

Hom.:

AF XY:

0.0000316

AC XY:

AN XY:

126590

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000552

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000229

AC:

AN:

1442444

Hom.:

Cov.:

AF XY:

0.0000237

AC XY:

AN XY:

717198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000281

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000491

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000166

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

May 20, 2024

The c.296A>G (p.E99G) 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 296, causing the glutamic acid (E) at amino acid position 99 to be replaced by a glycine (G). 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

0.078

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0055

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.31

M_CAP

Benign

0.0026

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.7

REVEL

Benign

0.027

Sift

Benign

0.18

Sift4G

Uncertain

0.015

Polyphen

0.0020

Vest4

0.12

MutPred

0.14

Loss of helix (P = 0.0444);

MVP

0.081

MPC

0.0042

ClinPred

0.045

GERP RS

3.0

Varity_R

0.066

gMVP

0.11

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