8-93728215-G-T

Variant names:

• chr8-93728215-G-T
• NM_145269.5:c.788G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145269.5(CIBAR1):​c.788G>T​(p.Cys263Phe) 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. 14/21 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)
• Consequence: CIBAR1 NM_145269.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.905
• Publications: 0 publications found

Genes affected

CIBAR1 (HGNC:30452): (CBY1 interacting BAR domain containing 1) Enables phospholipid binding activity. Involved in several processes, including inner mitochondrial membrane organization; limb morphogenesis; and membrane tubulation. Located in several cellular components, including centriole; ciliary base; and mitochondrial crista. [provided by Alliance of Genome Resources, Apr 2022]

RBM12B (HGNC:32310): (RNA binding motif protein 12B) Enables RNA binding activity. Predicted to be involved in regulation of RNA splicing. Predicted to be part of ribonucleoprotein complex. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1612744).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145269.5. 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
	CIBAR1	NM_145269.5	MANE Select	c.788G>T	p.Cys263Phe	missense	Exon 9 of 9	NP_660312.2	A1XBS5-1
	RBM12B	NM_001377960.1	MANE Select	c.*5190C>A		3_prime_UTR	Exon 4 of 4	NP_001364889.1	Q8IXT5
	CIBAR1	NM_001283034.2		c.674G>T	p.Cys225Phe	missense	Exon 8 of 8	NP_001269963.1	A1XBS5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIBAR1	ENST00000518322.6	TSL:5 MANE Select	c.788G>T	p.Cys263Phe	missense	Exon 9 of 9	ENSP00000429367.1	A1XBS5-1
	RBM12B	ENST00000520560.6	TSL:2 MANE Select	c.*5190C>A		3_prime_UTR	Exon 4 of 4	ENSP00000429807.2	Q8IXT5
	RBM12B	ENST00000517700.6	TSL:1	c.*5190C>A		3_prime_UTR	Exon 3 of 3	ENSP00000427729.2	Q8IXT5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	0.097
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.0078	T
Eigen	Benign	0.073
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.91
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.046
Sift	Benign	0.11	T
Sift4G	Benign	0.069	T
Polyphen		0.62	P
Vest4		0.18
MutPred		0.24		Gain of sheet (P = 0.039)
MVP		0.42
MPC		0.35
ClinPred		0.56	D
GERP RS		2.5
Varity_R		0.12
gMVP		0.095
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr8-94740443;