20-35980501-C-G

Variant names:

• chr20-35980501-C-G
• rs184047696
• NM_001365709.1:c.286C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001365709.1(CNBD2):​c.286C>G​(p.Pro96Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000973 in 1,614,198 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P96T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: CNBD2 NM_001365709.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04
• Publications: 2 publications found

Genes affected

CNBD2 (HGNC:16145): (cyclic nucleotide binding domain containing 2) Predicted to enable cAMP binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24037006).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365709.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNBD2	NM_001365709.1	MANE Select	c.286C>G	p.Pro96Ala	missense	Exon 4 of 12	NP_001352638.1	Q96M20-1
	CNBD2	NM_080834.4		c.286C>G	p.Pro96Ala	missense	Exon 4 of 12	NP_543024.2	Q96M20-2
	CNBD2	NM_001207076.3		c.286C>G	p.Pro96Ala	missense	Exon 4 of 11	NP_001194005.1	Q96M20-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNBD2	ENST00000373973.7	TSL:5 MANE Select	c.286C>G	p.Pro96Ala	missense	Exon 4 of 12	ENSP00000363084.3	Q96M20-1
	CNBD2	ENST00000538900.1	TSL:1	c.286C>G	p.Pro96Ala	missense	Exon 4 of 11	ENSP00000442729.1	Q96M20-3
	CNBD2	ENST00000463258.6	TSL:1	n.286C>G		non_coding_transcript_exon	Exon 4 of 9	ENSP00000476014.1	U3KQM1

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000107 AC: 27 AN: 251472 AF XY: 0.000132

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000149

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000882 AC: 129 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.000103 AC XY: 75 AN XY: 727236

African (AFR) AF: 0.000119 AC: 4 AN: 33478

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.0000710 AC: 79 AN: 1111982

Other (OTH) AF: 0.000265 AC: 16 AN: 60396

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74494

African (AFR) AF: 0.0000962 AC: 4 AN: 41578

American (AMR) AF: 0.000653 AC: 10 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68032

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000146 Hom.: 0

Bravo AF: 0.000272

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.24	T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		5.0
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.61
MVP		0.71
MPC		0.53
ClinPred		0.72	D
GERP RS		5.2
Varity_R		0.60
gMVP		0.33
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs184047696; hg19: chr20-34568423;