8-93726418-C-G

Variant names:

• chr8-93726418-C-G
• rs200002861
• NM_145269.5:c.682C>G

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.682C>G​(p.Pro228Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P228S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIBAR1 NM_145269.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 2 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]

CIBAR1 Gene-Disease associations (from GenCC):

• postaxial polydactyly type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• polydactyly, postaxial, type A9

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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=0.13128987).

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.682C>G	p.Pro228Ala	missense	Exon 8 of 9	NP_660312.2	A1XBS5-1
	CIBAR1	NM_001283034.2		c.568C>G	p.Pro190Ala	missense	Exon 7 of 8	NP_001269963.1	A1XBS5-2
	CIBAR1	NR_104267.2		n.780C>G		non_coding_transcript_exon	Exon 8 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIBAR1	ENST00000518322.6	TSL:5 MANE Select	c.682C>G	p.Pro228Ala	missense	Exon 8 of 9	ENSP00000429367.1	A1XBS5-1
	CIBAR1	ENST00000933184.1		c.658C>G	p.Pro220Ala	missense	Exon 7 of 8	ENSP00000603243.1
	CIBAR1	ENST00000423990.6	TSL:5	c.568C>G	p.Pro190Ala	missense	Exon 7 of 8	ENSP00000401774.2	A1XBS5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.95	T
PhyloP100		1.5
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.037
Sift	Benign	0.19	T
Sift4G	Benign	0.37	T
Polyphen		0.0080	B
Vest4		0.29
MutPred		0.31		Loss of stability (P = 0.0077)
MVP		0.53
MPC		0.14
ClinPred		0.62	D
GERP RS		1.6
Varity_R		0.039
gMVP		0.19
Mutation Taster		=78/22	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: rs200002861; hg19: chr8-94738646;