Genetic Variant CFLAR:c.*2020A>G (chr2-201138447-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000395148.6(CFLAR):c.*2020A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 850,946 control chromosomes in the GnomAD database, including 19,559 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 ( 5738 hom., cov: 32)

Exomes 𝑓: 0.18 ( 13821 hom. )

Consequence

CFLAR
ENST00000395148.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.285

Publications

10 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:

IMPDH1P10 (HGNC:33965): (inosine monophosphate dehydrogenase 1 pseudogene 10)

IMPDH1P10 links:

Genome browser will be placed here

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=-0.75).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7 link	c.524-1910A>G		intron_variant	Intron 4 of 9	ENST00000309955.8	NP_003870.4	O15519-1A0A024R3Y4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8 link	c.524-1910A>G		intron_variant	Intron 4 of 9	1	NM_003879.7	ENSP00000312455.2		O15519-1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37734

AN:

151918

Hom.:

5708

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.0119

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.229

GnomAD4 exome

AF:

0.185

AC:

129139

AN:

698910

Hom.:

13821

Cov.:

AF XY:

0.183

AC XY:

68880

AN XY:

376186

show subpopulations

African (AFR)

AF:

0.429

AC:

8165

AN:

19040

American (AMR)

AF:

0.127

AC:

5555

AN:

43770

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

5698

AN:

21436

East Asian (EAS)

AF:

0.00396

AC:

144

AN:

36356

South Asian (SAS)

AF:

0.130

AC:

9233

AN:

71270

European-Finnish (FIN)

AF:

0.141

AC:

6351

AN:

44914

Middle Eastern (MID)

AF:

0.204

AC:

587

AN:

2884

European-Non Finnish (NFE)

AF:

0.203

AC:

86259

AN:

423880

Other (OTH)

AF:

0.202

AC:

7147

AN:

35360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

6045

12089

18134

24178

30223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1098

2196

3294

4392

5490

<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:

0.249

AC:

37816

AN:

152036

Hom.:

5738

Cov.:

AF XY:

0.243

AC XY:

18026

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.423

AC:

17538

AN:

41438

American (AMR)

AF:

0.176

AC:

2693

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

980

AN:

3468

East Asian (EAS)

AF:

0.0120

AC:

AN:

5178

South Asian (SAS)

AF:

0.117

AC:

562

AN:

4824

European-Finnish (FIN)

AF:

0.133

AC:

1412

AN:

10600

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13853

AN:

67956

Other (OTH)

AF:

0.235

AC:

495

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1365

2730

4095

5460

6825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.243

Hom.:

635

Bravo

AF:

0.257

Asia WGS

AF:

0.114

AC:

400

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.0

(source)

DANN

Benign

0.42

PhyloP100

0.28

Mutation Taster

=99/1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over