dbSNP rs13413075: CFLAR:c.662-1363C>G (chr2-201147640-C-G) – 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.662-1363C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,914 control chromosomes in the GnomAD database, including 5,162 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 0.24 ( 5159 hom., cov: 31)

Exomes 𝑓: 0.29 ( 3 hom. )

Consequence

CFLAR
NM_003879.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.24

Publications

5 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=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 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.662-1363C>G	intron	N/A	NP_003870.4
CFLAR	NM_001127183.4		c.662-1363C>G	intron	N/A	NP_001120655.1	O15519-1
CFLAR	NM_001308042.3		c.662-1363C>G	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.662-1363C>G	intron	N/A	ENSP00000312455.2	O15519-1
CFLAR	ENST00000423241.6	TSL:1	c.662-1363C>G	intron	N/A	ENSP00000399420.2	O15519-1
CFLAR	ENST00000457277.5	TSL:1	c.662-1363C>G	intron	N/A	ENSP00000411535.1	O15519-11

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36809

AN:

151722

Hom.:

5140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.384

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.0398

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.289

AC:

AN:

Hom.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.273

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.243

AC:

36877

AN:

151838

Hom.:

5159

Cov.:

AF XY:

0.239

AC XY:

17706

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.384

AC:

15893

AN:

41366

American (AMR)

AF:

0.174

AC:

2657

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

967

AN:

3468

East Asian (EAS)

AF:

0.0401

AC:

207

AN:

5158

South Asian (SAS)

AF:

0.119

AC:

571

AN:

4812

European-Finnish (FIN)

AF:

0.161

AC:

1690

AN:

10522

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14194

AN:

67946

Other (OTH)

AF:

0.231

AC:

488

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1352

2703

4055

5406

6758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<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:

0.242

Hom.:

604

Bravo

AF:

0.248

Asia WGS

AF:

0.121

AC:

423

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.24

(source)

DANN

Benign

0.34

PhyloP100

-2.2

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