Variant 8-87286615-T-C 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.986T>C(p.Leu329Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000108 in 1,523,594 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 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

CNBD1
NM_173538.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

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 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=0.24792904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CNBD1	NM_173538.3 linkuse as main transcript	c.986T>C	p.Leu329Ser	missense_variant	8/11	ENST00000518476.6
CNBD1	XM_017013149.2 linkuse as main transcript	c.986T>C	p.Leu329Ser	missense_variant	8/11
CNBD1	XM_047421411.1 linkuse as main transcript	c.821T>C	p.Leu274Ser	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNBD1	ENST00000518476.6 linkuse as main transcript	c.986T>C	p.Leu329Ser	missense_variant	8/11	1	NM_173538.3
CNBD1	ENST00000523299.6 linkuse as main transcript	c.986T>C	p.Leu329Ser	missense_variant	8/13	3		P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000311

AC:

AN:

160952

Hom.:

AF XY:

0.0000354

AC XY:

AN XY:

84816

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:

0.0000789

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000114

AC:

157

AN:

1371440

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

678380

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:

0.000142

Gnomad4 OTH exome

AF:

0.000123

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000301

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000126

AC:

ExAC

AF:

0.0000102

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

Jun 12, 2023

The c.986T>C (p.L329S) alteration is located in exon 8 (coding exon 8) of the CNBD1 gene. This alteration results from a T to C substitution at nucleotide position 986, causing the leucine (L) at amino acid position 329 to be replaced by a serine (S). 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.38

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0067

T;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.97

L;.

MutationTaster

Benign

0.93

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.5

N;.

REVEL

Benign

0.17

Sift

Uncertain

0.0060

D;.

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;.

Vest4

0.61

MVP

0.30

MPC

0.017

ClinPred

0.56

GERP RS

5.5

Varity_R

0.19

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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