1-117025766-C-A

Variant names:

• chr1-117025766-C-A
• rs772514923
• NM_001256106.3:c.2686C>A

Variant summary

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

The NM_001256106.3(CD101):​c.2686C>A​(p.Leu896Ile) 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. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L896F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD101 NM_001256106.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.949
• Publications: 0 publications found

Genes affected

CD101 (HGNC:5949): (CD101 molecule) Predicted to enable hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides. Predicted to be involved in cell surface receptor signaling pathway. Predicted to act upstream of or within positive regulation of myeloid leukocyte differentiation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CD101-AS1 (HGNC:55665): (CD101 antisense RNA 1)

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=0.20312569).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256106.3. 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
	CD101	NM_001256106.3	MANE Select	c.2686C>A	p.Leu896Ile	missense	Exon 8 of 10	NP_001243035.1	Q93033
	CD101	NM_001256109.3		c.2686C>A	p.Leu896Ile	missense	Exon 8 of 10	NP_001243038.1	Q93033
	CD101	NM_004258.6		c.2686C>A	p.Leu896Ile	missense	Exon 8 of 10	NP_004249.2	Q93033

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD101	ENST00000682167.1	MANE Select	c.2686C>A	p.Leu896Ile	missense	Exon 8 of 10	ENSP00000508039.1	Q93033
	CD101	ENST00000369470.1	TSL:1	c.2686C>A	p.Leu896Ile	missense	Exon 8 of 10	ENSP00000358482.1	Q93033
	CD101	ENST00000256652.8	TSL:2	c.2686C>A	p.Leu896Ile	missense	Exon 8 of 9	ENSP00000256652.4	Q93033

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.95
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.18
Sift	Benign	0.67	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.16
MutPred		0.65		Loss of catalytic residue at L896 (P = 0.0047)
MVP		0.57
MPC		0.12
ClinPred		0.29	T
GERP RS		2.3
Varity_R		0.068
gMVP		0.083
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs772514923; hg19: chr1-117568388;