Genetic Variant CFLAR:c.387+104G>A (chr2-201133238-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003879.7(CFLAR):c.387+104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 755,868 control chromosomes in the GnomAD database, including 14 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 0.0030 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0041 ( 11 hom. )

Consequence

CFLAR
NM_003879.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0970

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BS2

High AC in GnomAd4 at 462 AD gene.

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.387+104G>A	intron	N/A	NP_003870.4
CFLAR	NM_001127183.4		c.387+104G>A	intron	N/A	NP_001120655.1
CFLAR	NM_001308042.3		c.387+104G>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.387+104G>A	intron	N/A	ENSP00000312455.2
CFLAR	ENST00000423241.6	TSL:1	c.387+104G>A	intron	N/A	ENSP00000399420.2
CFLAR	ENST00000457277.5	TSL:1	c.387+104G>A	intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes

AF:

0.00304

AC:

462

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00560

Gnomad OTH

AF:

0.00192

GnomAD4 exome

AF:

0.00412

AC:

2489

AN:

603554

Hom.:

AF XY:

0.00418

AC XY:

1327

AN XY:

317472

show subpopulations

African (AFR)

AF:

0.000950

AC:

AN:

15796

American (AMR)

AF:

0.000453

AC:

AN:

30900

Ashkenazi Jewish (ASJ)

AF:

0.0000556

AC:

AN:

17982

East Asian (EAS)

AF:

0.00

AC:

AN:

32062

South Asian (SAS)

AF:

0.00299

AC:

173

AN:

57948

European-Finnish (FIN)

AF:

0.00148

AC:

AN:

47214

Middle Eastern (MID)

AF:

0.000809

AC:

AN:

2472

European-Non Finnish (NFE)

AF:

0.00580

AC:

2135

AN:

368216

Other (OTH)

AF:

0.00255

AC:

AN:

30964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

118

236

355

473

591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00303

AC:

462

AN:

152314

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

199

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

41562

American (AMR)

AF:

0.000458

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00249

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00560

AC:

381

AN:

68028

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00359

Hom.:

Bravo

AF:

0.00295

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.7

(source)

DANN

Benign

0.81

PhyloP100

-0.097

PromoterAI

-0.013

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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