8-87237062-T-C

Variant names:

• chr8-87237062-T-C
• NM_173538.3:c.721T>C
• CNBD1 p.Phe241Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173538.3(CNBD1):​c.721T>C​(p.Phe241Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNBD1 NM_173538.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86
• Publications: 0 publications found

Genes affected

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

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04838246).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173538.3. 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
	CNBD1	NM_173538.3	MANE Select	c.721T>C	p.Phe241Leu	missense	Exon 6 of 11	NP_775809.1	Q8NA66

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNBD1	ENST00000518476.6	TSL:1 MANE Select	c.721T>C	p.Phe241Leu	missense	Exon 6 of 11	ENSP00000430073.1	Q8NA66
	CNBD1	ENST00000523299.6	TSL:3	c.721T>C	p.Phe241Leu	missense	Exon 6 of 13	ENSP00000430986.2	H0YC59
	CNBD1	ENST00000522105.1	TSL:3	n.235T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0030
DANN	Benign	0.47
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.11	N
PhyloP100		-2.9
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.0080
Sift	Benign	0.77	T
Sift4G	Benign	1.0	T
Varity_R		0.035
gMVP		0.16
Mutation Taster		=94/6	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-88249290;