chr2-201160737-C-G

Variant names:

• chr2-201160737-C-G
• rs1942891566
• NM_003879.7:c.1099C>G

Variant summary

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

The NM_003879.7(CFLAR):​c.1099C>G​(p.Leu367Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CFLAR NM_003879.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.238
• Publications: 0 publications found

Genes affected

CFLAR (HGNC:1876): (CASP8 and FADD like apoptosis regulator) The protein encoded by this gene is a regulator of apoptosis and is structurally similar to caspase-8. However, the encoded protein lacks caspase activity and appears to be itself cleaved into two peptides by caspase-8. Several transcript variants encoding different isoforms have been found for this gene, and partial evidence for several more variants exists. [provided by RefSeq, Feb 2011]

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=0.09042457).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003879.7. 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
	CFLAR	NM_003879.7	MANE Select	c.1099C>G	p.Leu367Val	missense	Exon 9 of 10	NP_003870.4
	CFLAR	NM_001127183.4		c.1099C>G	p.Leu367Val	missense	Exon 9 of 10	NP_001120655.1	O15519-1
	CFLAR	NM_001308042.3		c.1099C>G	p.Leu367Val	missense	Exon 9 of 10	NP_001294971.1	O15519-11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.1099C>G	p.Leu367Val	missense	Exon 9 of 10	ENSP00000312455.2	O15519-1
	CFLAR	ENST00000423241.6	TSL:1	c.1099C>G	p.Leu367Val	missense	Exon 9 of 10	ENSP00000399420.2	O15519-1
	CFLAR	ENST00000457277.5	TSL:1	c.1099C>G	p.Leu367Val	missense	Exon 8 of 9	ENSP00000411535.1	O15519-11

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

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	0.074
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Uncertain	0.97
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.24
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.082
Sift	Benign	0.29	T
Sift4G	Benign	0.34	T
Polyphen		0.32	B
Vest4		0.087
MutPred		0.49		Loss of sheet (P = 0.0457)
MVP		0.56
MPC		0.49
ClinPred		0.17	T
GERP RS		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.16
Mutation Taster		=87/13	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: rs1942891566; hg19: chr2-202025460;