dbSNP rs56863085: CFLAR:c.793+3089C>T (chr2-201152924-C-T) – 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+3089C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,210 control chromosomes in the GnomAD database, including 5,493 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 ( 5493 hom., cov: 32)

Exomes 𝑓: 0.22 ( 0 hom. )

Consequence

CFLAR
NM_003879.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.497

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:

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=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 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+3089C>T	intron	N/A	NP_003870.4
CFLAR	NM_001127183.4		c.793+3089C>T	intron	N/A	NP_001120655.1
CFLAR	NM_001308042.3		c.793+3089C>T	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+3089C>T	intron	N/A	ENSP00000312455.2
CFLAR	ENST00000423241.6	TSL:1	c.793+3089C>T	intron	N/A	ENSP00000399420.2
CFLAR	ENST00000457277.5	TSL:1	c.793+3089C>T	intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37665

AN:

152046

Hom.:

5472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.279

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:

0.228

GnomAD4 exome

AF:

0.217

AC:

AN:

Hom.:

Cov.:

AF XY:

0.265

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.188

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.248

AC:

37736

AN:

152164

Hom.:

5493

Cov.:

AF XY:

0.243

AC XY:

18085

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.401

AC:

16643

AN:

41474

American (AMR)

AF:

0.176

AC:

2696

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

969

AN:

3468

East Asian (EAS)

AF:

0.0405

AC:

210

AN:

5190

South Asian (SAS)

AF:

0.118

AC:

571

AN:

4828

European-Finnish (FIN)

AF:

0.161

AC:

1710

AN:

10590

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14230

AN:

68004

Other (OTH)

AF:

0.234

AC:

494

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1446

2892

4339

5785

7231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.245

Hom.:

646

Bravo

AF:

0.253

Asia WGS

AF:

0.125

AC:

436

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

3.8

(source)

DANN

Benign

0.39

PhyloP100

0.50

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