Variant 8-87206082-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173538.3(CNBD1):c.521A>G(p.His174Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CNBD1
NM_173538.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.74

Variant links:

Genes affected

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

CNBD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19430754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNBD1	NM_173538.3 link	c.521A>G	p.His174Arg	missense_variant	5/11	ENST00000518476.6	NP_775809.1	Q8NA66
CNBD1	XM_017013149.2 link	c.521A>G	p.His174Arg	missense_variant	5/11		XP_016868638.1
CNBD1	XM_024447082.2 link	c.521A>G	p.His174Arg	missense_variant	5/7		XP_024302850.1
CNBD1	XM_047421411.1 link	c.356A>G	p.His119Arg	missense_variant	4/7		XP_047277367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CNBD1	ENST00000518476.6 link	c.521A>G	p.His174Arg	missense_variant	5/11	1	NM_173538.3	ENSP00000430073.1	Q8NA66
CNBD1	ENST00000523299.6 link	c.521A>G	p.His174Arg	missense_variant	5/13	3		ENSP00000430986.2	H0YC59
CNBD1	ENST00000522105.1 link	n.35A>G		non_coding_transcript_exon_variant	1/2	3
CNBD1	ENST00000522427.1 link	n.264A>G		non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1454766

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723670

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000458

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Nov 12, 2024

The c.521A>G (p.H174R) alteration is located in exon 5 (coding exon 5) of the CNBD1 gene. This alteration results from a A to G substitution at nucleotide position 521, causing the histidine (H) at amino acid position 174 to be replaced by an arginine (R). 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

0.24

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0089

T;.

Eigen

Benign

0.0087

Eigen_PC

Benign

0.074

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.076

MetaRNN

Benign

0.19

T;T

MetaSVM

Uncertain

0.28

MutationAssessor

Benign

0.69

N;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.6

D;.

REVEL

Uncertain

0.30

Sift

Benign

0.099

T;.

Sift4G

Uncertain

0.044

D;T

Polyphen

0.60

P;.

Vest4

0.41

MutPred

0.27

Loss of ubiquitination at K173 (P = 0.0428);.;

MVP

0.36

MPC

0.0073

ClinPred

0.30

GERP RS

5.3

Varity_R

0.14

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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