Genetic Variant CFLAR:c.794-2628G>C (chr2-201157804-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.794-2628G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,090 control chromosomes in the GnomAD database, including 17,197 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 0.47 ( 17197 hom., cov: 33)

Exomes 𝑓: 0.20 ( 0 hom. )

Consequence

CFLAR
NM_003879.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.572

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=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 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.794-2628G>C	intron	N/A	NP_003870.4
CFLAR	NM_001127183.4		c.794-2628G>C	intron	N/A	NP_001120655.1	O15519-1
CFLAR	NM_001308042.3		c.794-2628G>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.794-2628G>C	intron	N/A	ENSP00000312455.2	O15519-1
CFLAR	ENST00000423241.6	TSL:1	c.794-2628G>C	intron	N/A	ENSP00000399420.2	O15519-1
CFLAR	ENST00000457277.5	TSL:1	c.794-2628G>C	intron	N/A	ENSP00000411535.1	O15519-11

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71620

AN:

151962

Hom.:

17175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.492

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.463

GnomAD4 exome

AF:

0.200

AC:

AN:

Hom.:

Cov.:

AF XY:

0.200

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.471

AC:

71684

AN:

152080

Hom.:

17197

Cov.:

AF XY:

0.465

AC XY:

34524

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.457

AC:

18945

AN:

41480

American (AMR)

AF:

0.412

AC:

6286

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.533

AC:

1849

AN:

3468

East Asian (EAS)

AF:

0.248

AC:

1283

AN:

5176

South Asian (SAS)

AF:

0.347

AC:

1678

AN:

4832

European-Finnish (FIN)

AF:

0.492

AC:

5192

AN:

10544

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.514

AC:

34959

AN:

67992

Other (OTH)

AF:

0.469

AC:

990

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1863

3725

5588

7450

9313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<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:

0.380

Hom.:

1070

Bravo

AF:

0.464

Asia WGS

AF:

0.314

AC:

1094

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.7

(source)

DANN

Benign

0.47

PhyloP100

-0.57

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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