Genetic Variant CFLAR:c.793+470G>T (chr2-201150305-G-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+470G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 150,912 control chromosomes in the GnomAD database, including 5,025 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 ( 5021 hom., cov: 29)

Exomes 𝑓: 0.15 ( 4 hom. )

Consequence

CFLAR
NM_003879.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.901

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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 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.793+470G>T	intron	N/A	NP_003870.4
CFLAR	NM_001127183.4		c.793+470G>T	intron	N/A	NP_001120655.1	O15519-1
CFLAR	NM_001308042.3		c.793+470G>T	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.793+470G>T	intron	N/A	ENSP00000312455.2	O15519-1
CFLAR	ENST00000423241.6	TSL:1	c.793+470G>T	intron	N/A	ENSP00000399420.2	O15519-1
CFLAR	ENST00000457277.5	TSL:1	c.793+470G>T	intron	N/A	ENSP00000411535.1	O15519-11

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36139

AN:

150332

Hom.:

5002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.0392

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.149

AC:

AN:

464

Hom.:

Cov.:

AF XY:

0.148

AC XY:

AN XY:

344

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.143

AC:

AN:

European-Finnish (FIN)

AF:

0.200

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.146

AC:

AN:

336

Other (OTH)

AF:

0.214

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

GnomAD4 genome

AF:

0.241

AC:

36205

AN:

150448

Hom.:

5021

Cov.:

AF XY:

0.236

AC XY:

17291

AN XY:

73418

show subpopulations

African (AFR)

AF:

0.381

AC:

15472

AN:

40642

American (AMR)

AF:

0.174

AC:

2620

AN:

15098

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

962

AN:

3460

East Asian (EAS)

AF:

0.0395

AC:

203

AN:

5140

South Asian (SAS)

AF:

0.117

AC:

560

AN:

4792

European-Finnish (FIN)

AF:

0.155

AC:

1598

AN:

10316

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.208

AC:

14099

AN:

67716

Other (OTH)

AF:

0.231

AC:

483

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1197

2394

3591

4788

5985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.131

Hom.:

235

Bravo

AF:

0.248

Asia WGS

AF:

0.120

AC:

421

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.91

(source)

DANN

Benign

0.27

PhyloP100

-0.90

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