Variant 2-201129887-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003879.7(CFLAR):c.22C>G(p.Gln8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CFLAR
NM_003879.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

Variant links:

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]

CFLAR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26311958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFLAR	NM_003879.7 linkuse as main transcript	c.22C>G	p.Gln8Glu	missense_variant	2/10	ENST00000309955.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFLAR	ENST00000309955.8 linkuse as main transcript	c.22C>G	p.Gln8Glu	missense_variant	2/10	1	NM_003879.7	P2	O15519-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251402

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.22C>G (p.Q8E) alteration is located in exon 2 (coding exon 1) of the CFLAR gene. This alteration results from a C to G substitution at nucleotide position 22, causing the glutamine (Q) at amino acid position 8 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.28

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.34

T;.;.;.;.;T;.;T;T;.;.;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.031

MetaRNN

Benign

0.26

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.8

L;L;L;L;.;.;.;L;.;.;L;L

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

N;N;N;N;N;N;D;N;D;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.13

T;T;D;T;T;T;D;T;D;D;T;T

Sift4G

Uncertain

0.0090

D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;P;D;P;B;.;.;D;.;.;P;D

Vest4

0.45

MutPred

0.48

Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);

MVP

0.60

MPC

2.4

ClinPred

0.45

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.45

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over