Genetic Variant CFLAR:c.793+2850G>A (chr2-201152685-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003879.7(CFLAR):c.793+2850G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,142 control chromosomes in the GnomAD database, including 2,979 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2978 hom., cov: 32)

Exomes 𝑓: 0.15 ( 1 hom. )

Consequence

CFLAR
NM_003879.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.78

Publications

6 publications found

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:

CFLAR-AS1 (HGNC:14437): (CFLAR antisense RNA 1)

CFLAR-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CFLAR	NM_003879.7	MANE Select	c.793+2850G>A	intron	N/A	NP_003870.4
CFLAR	NM_001127183.4		c.793+2850G>A	intron	N/A	NP_001120655.1
CFLAR	NM_001308042.3		c.793+2850G>A	intron	N/A	NP_001294971.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.793+2850G>A	intron	N/A	ENSP00000312455.2
CFLAR	ENST00000423241.6	TSL:1	c.793+2850G>A	intron	N/A	ENSP00000399420.2
CFLAR	ENST00000457277.5	TSL:1	c.793+2850G>A	intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27612

AN:

151976

Hom.:

2977

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.0353

Gnomad SAS

AF:

0.0454

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.178

GnomAD4 exome

AF:

0.146

AC:

AN:

Hom.:

AF XY:

0.184

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.200

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.182

AC:

27626

AN:

152094

Hom.:

2978

Cov.:

AF XY:

0.178

AC XY:

13245

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.296

AC:

12290

AN:

41456

American (AMR)

AF:

0.140

AC:

2135

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

574

AN:

3470

East Asian (EAS)

AF:

0.0356

AC:

184

AN:

5174

South Asian (SAS)

AF:

0.0452

AC:

218

AN:

4818

European-Finnish (FIN)

AF:

0.121

AC:

1281

AN:

10608

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.153

AC:

10427

AN:

67974

Other (OTH)

AF:

0.176

AC:

371

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1148

2296

3444

4592

5740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.172

Hom.:

438

Bravo

AF:

0.190

Asia WGS

AF:

0.0590

AC:

208

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over