8-87237041-A-G

Position:

• chr8-87237041-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173538.3(CNBD1):​c.700A>G​(p.Ser234Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,120 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CNBD1 NM_173538.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55

Genes affected

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

ACMG classification

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=0.081146866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNBD1	NM_173538.3	c.700A>G	p.Ser234Gly	missense_variant	6/11	ENST00000518476.6
CNBD1	XM_017013149.2	c.700A>G	p.Ser234Gly	missense_variant	6/11
CNBD1	XM_024447082.2	c.700A>G	p.Ser234Gly	missense_variant	6/7
CNBD1	XM_047421411.1	c.535A>G	p.Ser179Gly	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNBD1	ENST00000518476.6	c.700A>G	p.Ser234Gly	missense_variant	6/11	1	NM_173538.3
CNBD1	ENST00000523299.6	c.700A>G	p.Ser234Gly	missense_variant	6/13	3		P1
CNBD1	ENST00000522105.1	n.214A>G		non_coding_transcript_exon_variant	2/2	3
CNBD1	ENST00000522427.1	n.443A>G		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460120 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726384

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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.: 32

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

Jun 29, 2023

The c.700A>G (p.S234G) alteration is located in exon 6 (coding exon 6) of the CNBD1 gene. This alteration results from a A to G substitution at nucleotide position 700, causing the serine (S) at amino acid position 234 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	0.074
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.8
DANN	Benign	0.33
DEOGEN2	Benign	0.00026	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.48	N;.
REVEL	Benign	0.017
Sift	Benign	0.20	T;.
Sift4G	Benign	0.67	T;T
Polyphen		0.0010	B;.
Vest4		0.18
MutPred		0.25		Loss of helix (P = 0.0558);.;
MVP		0.067
MPC		0.0048
ClinPred		0.024	T
GERP RS		0.53
Varity_R		0.038
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-88249269;