Genetic Variant CFLAR:c.712-239G>C (chr2-201149515-G-C) – 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.712-239G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 365,116 control chromosomes in the GnomAD database, including 9,881 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 0.25 ( 5667 hom., cov: 32)

Exomes 𝑓: 0.18 ( 4214 hom. )

Consequence

CFLAR
NM_003879.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34

Publications

7 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 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	UniProt
CFLAR	NM_003879.7	MANE Select	c.712-239G>C	intron	N/A	NP_003870.4
CFLAR	NM_001127183.4		c.712-239G>C	intron	N/A	NP_001120655.1	O15519-1
CFLAR	NM_001308042.3		c.712-239G>C	intron	N/A	NP_001294971.1	O15519-11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.712-239G>C	intron	N/A	ENSP00000312455.2	O15519-1
CFLAR	ENST00000423241.6	TSL:1	c.712-239G>C	intron	N/A	ENSP00000399420.2	O15519-1
CFLAR	ENST00000457277.5	TSL:1	c.712-239G>C	intron	N/A	ENSP00000411535.1	O15519-11

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38145

AN:

151980

Hom.:

5646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.413

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.0402

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.231

GnomAD4 exome

AF:

0.182

AC:

38685

AN:

213018

Hom.:

4214

Cov.:

AF XY:

0.179

AC XY:

20134

AN XY:

112396

show subpopulations

African (AFR)

AF:

0.400

AC:

2423

AN:

6058

American (AMR)

AF:

0.139

AC:

1108

AN:

7956

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

1766

AN:

6966

East Asian (EAS)

AF:

0.0159

AC:

238

AN:

14926

South Asian (SAS)

AF:

0.120

AC:

2368

AN:

19670

European-Finnish (FIN)

AF:

0.157

AC:

1808

AN:

11548

Middle Eastern (MID)

AF:

0.180

AC:

177

AN:

982

European-Non Finnish (NFE)

AF:

0.199

AC:

26276

AN:

132212

Other (OTH)

AF:

0.199

AC:

2521

AN:

12700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1504

3008

4513

6017

7521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.251

AC:

38214

AN:

152098

Hom.:

5667

Cov.:

AF XY:

0.246

AC XY:

18317

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.413

AC:

17106

AN:

41420

American (AMR)

AF:

0.177

AC:

2703

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

971

AN:

3472

East Asian (EAS)

AF:

0.0405

AC:

210

AN:

5182

South Asian (SAS)

AF:

0.118

AC:

570

AN:

4822

European-Finnish (FIN)

AF:

0.161

AC:

1709

AN:

10590

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14231

AN:

68006

Other (OTH)

AF:

0.237

AC:

501

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1402

2804

4206

5608

7010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.136

Hom.:

245

Bravo

AF:

0.257

Asia WGS

AF:

0.125

AC:

438

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.22

(source)

DANN

Benign

0.53

PhyloP100

-1.3

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over