8-87206028-T-C

Position:

• chr8-87206028-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173538.3(CNBD1):​c.467T>C​(p.Val156Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,444,210 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CNBD1 NM_173538.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64

Genes affected

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

CNBD1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNBD1	NM_173538.3	c.467T>C	p.Val156Ala	missense_variant	5/11	ENST00000518476.6	NP_775809.1
CNBD1	XM_017013149.2	c.467T>C	p.Val156Ala	missense_variant	5/11		XP_016868638.1
CNBD1	XM_024447082.2	c.467T>C	p.Val156Ala	missense_variant	5/7		XP_024302850.1
CNBD1	XM_047421411.1	c.302T>C	p.Val101Ala	missense_variant	4/7		XP_047277367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNBD1	ENST00000518476.6	c.467T>C	p.Val156Ala	missense_variant	5/11	1	NM_173538.3	ENSP00000430073.1
CNBD1	ENST00000523299.6	c.467T>C	p.Val156Ala	missense_variant	5/13	3		ENSP00000430986.2
CNBD1	ENST00000522427.1	n.210T>C		non_coding_transcript_exon_variant	2/4	4
CNBD1	ENST00000522105.1	n.-20T>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444210 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717582

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: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 30, 2024

The c.467T>C (p.V156A) alteration is located in exon 5 (coding exon 5) of the CNBD1 gene. This alteration results from a T to C substitution at nucleotide position 467, causing the valine (V) at amino acid position 156 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	Uncertain	0.51
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.37	T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	0.90	L;.
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.1	D;.
REVEL	Uncertain	0.47
Sift	Uncertain	0.0050	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.67
MutPred		0.37		Gain of catalytic residue at V156 (P = 0.0099);.;
MVP		0.38
MPC		0.012
ClinPred		0.95	D
GERP RS		5.3
Varity_R		0.18
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs1404442288; hg19: chr8-88218256;