Variant 8-87284702-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.796A>G(p.Thr266Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,604,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CNBD1
NM_173538.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.506

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=0.060684085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNBD1	NM_173538.3 linkuse as main transcript	c.796A>G	p.Thr266Ala	missense_variant	7/11	ENST00000518476.6	NP_775809.1	Q8NA66
CNBD1	XM_017013149.2 linkuse as main transcript	c.796A>G	p.Thr266Ala	missense_variant	7/11		XP_016868638.1
CNBD1	XM_047421411.1 linkuse as main transcript	c.631A>G	p.Thr211Ala	missense_variant	6/7		XP_047277367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CNBD1	ENST00000518476.6 linkuse as main transcript	c.796A>G	p.Thr266Ala	missense_variant	7/11	1	NM_173538.3	ENSP00000430073.1	Q8NA66
CNBD1	ENST00000523299.6 linkuse as main transcript	c.796A>G	p.Thr266Ala	missense_variant	7/13	3		ENSP00000430986.2	H0YC59
CNBD1	ENST00000522427.1 linkuse as main transcript	n.539A>G		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.000114

AC:

AN:

149452

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000494

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:

0.0000987

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000207

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000117

AC:

AN:

238908

Hom.:

AF XY:

0.000108

AC XY:

AN XY:

129272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000604

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000473

Gnomad NFE exome

AF:

0.000230

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

202

AN:

1454568

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

723020

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.0000457

Gnomad4 ASJ exome

AF:

0.0000388

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000173

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.000114

AC:

AN:

149576

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

72842

show subpopulations

Gnomad4 AFR

AF:

0.0000492

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000987

Gnomad4 NFE

AF:

0.000207

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000187

Hom.:

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000829

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

Apr 04, 2024

The c.796A>G (p.T266A) alteration is located in exon 7 (coding exon 7) of the CNBD1 gene. This alteration results from a A to G substitution at nucleotide position 796, causing the threonine (T) at amino acid position 266 to be replaced by an alanine (A). 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

0.19

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.035

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.49

T;T

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.061

T;T

MetaSVM

Uncertain

0.043

MutationAssessor

Benign

0.97

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.6

D;.

REVEL

Benign

0.19

Sift

Uncertain

0.015

D;.

Sift4G

Uncertain

0.033

D;D

Polyphen

0.13

B;.

Vest4

0.45

MVP

0.12

MPC

0.0092

ClinPred

0.036

GERP RS

-0.011

Varity_R

0.090

gMVP

0.17

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