CFLAR p.Leu367Leu

Variant names:

• chr2-201160736-G-G
• NM_003879.7:c.

Your query was ambiguous. Multiple possible variants found:

• chr2-201160737--
• chr2-201160737-C-T
• chr2-201160739-G-T
• chr2-201160739-G-C
• chr2-201160739-G-A
• chr2-201160737-CTG-TTA

Variant summary

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

The NM_003879.7(CFLAR):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.		intron	N/A	NP_001120655.1	O15519-1
	CFLAR	NM_001308042.3		c.		intron	N/A	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.		splice_donor intron	N/A	ENSP00000312455.2	O15519-1
	CFLAR	ENST00000423241.6	TSL:1	c.		splice_donor intron	N/A	ENSP00000399420.2	O15519-1
	CFLAR	ENST00000457277.5	TSL:1	c.		splice_donor intron	N/A	ENSP00000411535.1	O15519-11

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24

Splicing

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: chr2-202025459;